Severe aplastic anemia and not a candidate for allogeneic transplant because of his age. Antisuppressants seem to be the most suitable.

A 71-year-old man presenting with severe pancytopenia without presence of immature cells and with a bone marrow study suggestive of severe aplastic anemia. What would be the fundamental therapeutic approach?

Treatment with methylprednisolone at a dose of 1 g/kg/day for 5 days.

Study of siblings and if any of them is HLA compatible, allogeneic transplantation of hematopoietic progenitors.

Immunosuppressive therapy with cyclosporine and antithymocyte immunoglobulin.

Chemotherapy and if response autologous transplantation of hematopoietic progenitors.

Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome.

In most patients, aplastic anemia results from T-cell-mediated immune destruction of bone marrow. Aplastic anemia can be effectively treated by stem cell transplantation or immunosuppression. To assess long-term outcomes after immunosuppressive therapy. Cohort of 122 patients (31 were < or =18 years and 91 were >18 years) with severe aplastic anemia, as determined by bone marrow cellularity and blood cell count criteria, were enrolled in a single-arm interventional research protocol from 1991 to 1998 at a federal government research hospital. A dose of 40 mg/kg per day of antithymocyte globulin administered for 4 days, 10 to 12 mg/kg per day of cyclosporine for 6 months (adjusted for blood levels), and a short course of corticosteroids (1 mg/d of methylprednisolone for about 2 weeks). Survival, improvement of pancytopenia and transfusion-independence, relapse, and evolution to other hematologic diseases. Response rates were 60% at 3 months after initiation of treatment, 61% at 6 months, and 58% at 1 year. The blood cell counts of patients who responded no longer satisfied severity criteria and they were transfusion-independent. Overall actuarial survival at 7 years was 55%. Survival was associated with early satisfaction of response criteria (86% vs 40% at 5 years; P<.001) and by blood counts at 3 months (reticulocyte count or platelet count of >50 x 10(3)/ microL predicted survival at 5 years of 90% [64/71] vs 42% [12/34] for patients with less robust recovery [P<.001 by log-rank test]). There were no deaths among responders more than 3 years after treatment. Relapse was common, but severe pancytopenia usually did not recur. Relapse did not influence survival. Thirteen patients showed evolution to other hematologic diseases, including monosomy 7. Approximately half of patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine have durable recovery and excellent long-term survival. These outcomes were related to the quality of hematologic recovery.

[Second allogenic bone marrow transplantation after late graft rejection in a patient with severe aplastic anemia].

Allogeneic bone marrow transplantation (BMT) is the treatment of choice in young patients (pts) with severe aplastic anemia (SAA) who have an HLA identical sibling donor. Late graft rejection to following allogeneic BMT for SAA is a significant clinical problem and is associated with a high risk of mortality. The optimal treatment strategy for patients with late graft rejection after first BMT is still an open question. We report 12-year-old patient with acquired SAA who underwent BMT from his HLA identical sister. BMT was first-line treatment within 3 months of diagnosis. Preparative therapy was Cyclophosphamide (Cy) 200 mg/kg body mass (BM) during 4 days. Graft versus host disease (GVHD) was prevented with Methotrexate (MTX), Methylprednisolone (MPDN) and Cyclosporin A (CsA). After 17 months, during which patient was with normal blood counts and full donor chimaerism, graft rejection occurred. The patient was re-engrafted from the same donor after conditioning with Cy 200 mg/kg BM plus horse antithymocyte globulin (ATG)--2 vials (á 25 mg)/10 kg BM over 4 days. Before the collection, donor's bone marrow was activated with low dose rhGM-CSF (3 micrograms/kg one day). Following a secondary BMT engraftment has sustained. The patient is alive with full donor chimaerism 26 months from secondary transplantation, without acute or chronic GVHD.

[Hematopoietic stem-cell transplantation in aplastic anemia].

Severe aplastic anemia is a rare syndrome characterized by bone marrow failure with cytopenias and hypocellular bone marrow biopsy (usually 10-15%), without blasts or myelodysplasia. The first choice treatment for these patients is allogeneic bone marrow transplantation from a sibling matched for HLA-A, HLA-B and HLA-DR. Unfortunately only 30% of patients have an HLA-matched sibling (a 25% chance per sibling). The alternative treatment for severe aplastic anemia for the rest of the patients (70%) is immunosuppression with antithymocyte globuline and cyclosporine. The evolution of bone marrow transplantation since 1970's has been positive in terms of survival and transplant success (initial overall survival 43% vs. 90% lately, and graft rejection of 29% vs. 4%). The favorable outcome of bone marrow transplantation for severe or very severe aplastic anemia is due to: the use of conditioning with antithymocyte globuline and cyclophosphamide, the use of graft-vs.-host disease prophylaxis with short curse methotrexate and cyclosporine and the use of filtrated and irradiated blood products. For those patients without an HLA-matched related donor the first treatment to use is the immunosuppression with antithymocyte globuline and cyclosporine. Another option emerged in the late 80's is the unrelated bone marrow transplantation, with survival hardly half of the HLA-identical related bone marrow transplants. In our country, the first allogeneic bone marrow transplant was done in the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, in a patient with aplastic anemia, making possible to perform this procedure safely in our country.

Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution.

We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6--9), and the median time between diagnosis and transplant 1 month (range, 1--4). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days--7 to--4 and antithymocyte globulin (30 mg/kg per day) on days--4 to--2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 x 10(6) and 0.3 x 10(6)/kg, respectively. The median time taken to achieve a neutrophil count >0.5 x 10(9)/l was 12 days and to recover a platelet count >20 x 10(9)/l, 13 days. Two patients developed acute GVHD grade I--II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4--3), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.

Allogeneic hematopoietic stem cell transplantation is superior to immunosuppressive therapy in Indian children with aplastic anemia--a single-center analysis of 100 patients.

The authors compared the outcome in 100 children (61 boys, 39 girls; median age of 10.1 +/- 3.4 years) with aplastic anemia who underwent either immunosuppressive therapy (IST; n = 70) or hematopoietic stem cell transplantation (HSCT; n = 30) between 1998 and 2007. Conditioning regimes for HSCT were a combination of either cyclophosphamide (Cy) with antilymphocyte globulin (ALG) or fludarabine (Flu) with Cy or busulfan (Bu) +/- antithymocyte globulin (ATG). Stem cell source was bone marrow in 20 and peripheral blood stem cells (PBSCs) in 10. Patients undergoing IST received either equine ALG or ATG in combination with steroids and cyclosporine. Primary engraftment was seen in 25 children (83.3%), with acute graft-versus-host disease (aGvHD) in 5 (16.6%). The day 100 transplant-related mortality (TRM) was 30% and at a median follow up of 36 months (range: 6-197), the overall and disease-free survival is 70%. Among children who received IST, 60 children received ALG while 10 received ATGAM. Responses were seen in 27 children (43.5%), which was complete (CR) in 12 and partial (PR) in 15. At a median follow up of 38 months (range: 1-84), the overall survival is 37.1%, with 81.4% survival among responders and <10% survival among non-responders. HSCT would be the treatment of choice in children with severe aplastic anemia who have a human leukocyte antigen (HLA)-matched related donor and is superior to IST in this series from India.

Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia.

Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia.

[The use of allogeneic bone marrow transplantation and immunosuppressive therapy in the treatment of patients with acquired aplastic anemia].

To evaluate the efficiency of related and unrelated allogeneic bone marrow transplantation (alloBMT) versus immunosuppressive therapy (IST) in patients with aplastic anemia (AA) having no HLA-compatible bone marrow donor. The study covered 61 patients (34 men and 27 women) diagnosed as having acquired AA. Of them, 51 patients were diagnosed as having severe AA, 5 had supersevere AA, and 5 had non-severe AA. Combined IST (antithymocyte globulin (ATG) + cyclosporin A (CsA)) was used in 43 patients; allo-BMT was performed in 18. The basic types of ATG (ATGAM (Pfizer), thymoglobulin (Genzim), ATG (Fresenius), and goat antilymphocyte globulin (ALG) (Research Institute of Gerontology, Ministry of Health of the Russian Federation) were administered. CsA was given in a dose of 5 mg/kg/day. The standard conditioning regimen (ATGAM + cyclophosphanum) and fludarabine-containing (fludarabine + cyclophosphanum + ATG; busulfan + fludarabine + ATG) programs were used in the allo-BMT group. A combination of CsA and metothrexate was given to prevent a graft-versus-host reaction. Among the IST-receiving patients, overall survival (OS) was 71%. After the first course of IST by follow-up month 6, the response rate was 74%. The second course of IST was performed in 7 patients unresponsive after the first-line IST and in 8 patients with recurrent AA. After the second course of IST, the response rate was 46.7%. Four patients who failed to achieve remission after 2 courses of IST received its third course. A complete response was obtained in 3 patients. In 18 patients following allo-BMT (related and unrelated), OS was 86%; event-free survival was 65. In 12 patients after related allo-BMT, OS was 91.7%. Related allo-BMT is the method of choice if there is a HLA-compatible sibling. If there are contraindications to it or no related donor, IST with ATG + CsA is indicated. Ineffective IST is an indication for unrelated allo-BMT that may be recommended as life-saving therapy for young patients under 40 years of age.

Aplastic anemia

Treatment Treating immune-mediated aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine or, in more severe cases, a bone marrow transplant, a potential cure. The transplanted bone marrow replaces the failing bone marrow cells with new ones from a matching donor. The multipotent stem cells in the bone marrow reconstitute all three blood cell lines, giving the patient a new immune system, red blood cells, and platelets. However, besides the risk of graft failure, there is also a risk that the newly created white blood cells may attack the rest of the body ("graft-versus-host disease"). In young patients with an HLA-matched sibling donor, bone marrow transplant can be considered as a first-line treatment. Patients lacking a matched sibling donor typically pursue immunosuppression as a first-line treatment, and matched, unrelated donor transplants are considered second-line therapy.

Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.

To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.

[Outcome of allogeneic hematopoietic stem cell transplantation from HLA-matched sibling donor for 41 cases of severe aplastic anemia].

To evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA). The clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)×10(6)/kg in allo-BMT and 2.95 (1.27 - 5.98)×10(6)/kg in allo-PBSCT, respectively. Hematopoietic reconstitution was observed in all 41 patients (100%). The median time of neutrophils (ANC) reached to 0.5×10(9)/L and platelets (PLT) reached to 20×10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79) months. 36 patients survived. 5-year estimated overall survival (OS), disease free survival (DFS), and transplant-related mortality (TRM) was (81.1 ± 9.0)%, (68.4 ± 11.0)%, and (18.9 ± 9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34(+) cells no more than 2.5×10(6)/kg, the number of red blood cell (RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34(+) cells no more than 2.5× 10(6)/kg (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation (P = 0.038). MSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34(+) cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.

Bone marrow

Donation and transplantation In a bone marrow transplant, hematopoietic stem cells are removed from a person and infused into another person (allogenic) or into the same person at a later time (autologous). If the donor and recipient are compatible, these infused cells will then travel to the bone marrow and initiate blood cell production. Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases, such as congenital defects, autoimmune diseases or malignancies. The patient's own marrow is first killed off with drugs or radiation, and then the new stem cells are introduced. Before radiation therapy or chemotherapy in cases of cancer, some of the patient's hematopoietic stem cells are sometimes harvested and later infused back when the therapy is finished to restore the immune system.

Hematopoietic stem cell transplantation

Nonmyeloablative A newer treatment approach, nonmyeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone-marrow cells of the recipient. Instead, nonmyeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse. Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants. This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space.

[Treatment of acquired severe aplastic anemia in pediatric patients with immunosuppression and allogeneic stem cell hematopoietic transplant].

Severe acquired aplastic anemia (SAA) is an uncommon disease of childhood. Patients with SAA receive supportive care with transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be allogenic stem cell transplantation (SCT) from a matched sibling or immunosuppressive therapy (IT). To report the experience in the management of SAA. Twenty five children with acquired SAA were treated from July 1992 to September 2005. Patients with full matched sibling donors received allogenic SCT after conditioning with a cyclophosphamide containing regimen. The other patients received immune suppression with cyclosporine plus methylprednisolone (n= 18) plus ATG (n=17). All received supportive care until recovery of hematopoietic function. Those who had severe opportunistic infections at diagnosis or did not respond to two cycles of ATG were evaluated for unrelated donor SCT. Seven patients received sibling donor SCT and 18 IT, which was repeated in six. Three patients received mismatched related (1) or unrelated (2) SCT. Nineteen patients survived with a median follow up time of 4 years, 14 with full hematologic recovery. Six patients died: four due to infections after IT or SCT, one due to intracranial hemorrhage and one with secondary myelodysplasia 12 years after IT. Most children with SAA can be treated successfully with sibling donor SCT or IT. Patients without a histocompatible sibling who fail to respond to IS have a worse prognosis.

Aplastic anemia

Aplastic anemia can be definitively diagnosed by bone marrow biopsy. Normal bone marrow has 30–70% blood stem cells, but in aplastic anemia, these cells are mostly gone and are replaced by fat. First-line treatment for aplastic anemia consists of immunosuppressive drugs—typically either anti-lymphocyte globulin or anti-thymocyte globulin—combined with corticosteroids, chemotherapy, and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related, matched marrow donor. Aplastic anemia is known to have caused the deaths of Eleanor Roosevelt and Marie Curie. Signs and symptoms Anemia may lead to fatigue, pale skin, severe bruising, and a fast heart rate. Low platelets are associated with an increased risk of bleeding, bruising, and petechiae, with lower blood counts that impact the ability of the blood to clot. Low white blood cells increase the risk of infections.

Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies.

Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine-mobilized blood progenitor cells in allogeneic transplant recipients are rare. This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 x 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 x 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.

First successful allogeneic hematopoietic stem cell transplantation for a sickle cell disease patient in a low resource country (Nigeria): a case report.

Sickle cell disease (SCD) has a prevalence of 2-3% in Nigeria (population: over 150 million). We present our first allogeneic hematopoietic stem cell transplantation (HSCT) for a 7-year-old patient with severe sickle cell anemia and debilitating right-sided hemi-paraparesis. Conditioning was with (Reduced Intensity Conditioning (FLU/BU).[Fludarabine 160 mg/m2 (days -6 to -2) and Busulphan 16 mg/kg (4×25 mg 6 hly days -5 to -2) and Anti-thymocyte globulin(ATG)(ATGAM) total dose 500 mg (days -6 to -4)]. Graft versus Host Disease (GVHD) prophylaxis was with Cyclosporine A (2×50 mg daily) and Mycophenolate Mofetil (2×500 mg/day). Stem cell source was bone marrow harvested on the 28 September 2011 with 9.8×108 nucleated cells/kg in a total volume of 900 mL from his 14-year-old HLA-matched sibling (6/6). Neutrophil and platelet engraftment was day +18 and +21, respectively. At day +70 full blood count was a total white blood cell count of 3100/µl, absolute Neutrophil count 1200/µl, Hemoglobin (Hb) 11.3 g/dl, Platelet 198,000/µl, Hemoglobin phenotype AA, and no acute or chronic GVHD. He is clinically stable with a Chimerism at 2 years post-HSCT of 95% and responding to physiotherapy. We have successfully performed a stem cell transplanted in a 7-year-old Sickle Cell Anemia case. With the assistance of Government and improved Health Insurance Policy, we could make HSCT available as a cure for many Nigerians with both malignant and non-malignant disorders.

Management of the refractory aplastic anemia patient: what are the options?

Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.

Hematopoietic stem cell transplantation

Myeloablative The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSCs and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants, a combination of cyclophosphamide with total body irradiation is conventionally employed. This treatment also has an immunosuppressive effect that prevents rejection of the HSCs by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. In certain leukemias, though, this can coincide with protection against cancer relapse owing to the graft-versus-tumor effect. Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.

Successful Bone Marrow Recovery After an Immunoablative Regimen With Autologous Cord Blood Transplant in a Child With Idiopathic Severe Aplastic Anemia: A Case Report.

Aplastic anemia is a rare disease that manifests as bone marrow failure. The current treatment options include immunoablative therapy or allogeneic hematopoietic stem cell transplantation. We report a successful immunoablative regimen with autologous umbilical cord blood (auto-UCB) transplant in a 3-year-old boy with severe aplastic anemia. The immunoablation procedure consisted of 5 × 3.75 mg/kg antithymocyte globulin (Thymoglobulin) (total 18.75 mg/kg), methylprednisolone for 4 days, and cyclosporine A. The patient received auto-UCB containing 0.3 × 10<sup5</sup CD34<sup+</sup cells per kilogram of body weight. Recovery of leukocyte count above 1000/μL was reached on post-transplant day +39, and recovery of granulocytes above 500/μL was reached on day +40. The final regular transfusions of packed red blood cells and platelet concentrate were performed on day +55. The complications that occurred in the post-transplant period were nausea, diarrhea, septic fever, and hepatic abscess formation. Post-transplant immunosuppression with cyclosporine A was discontinued 17.5 months after auto-UCB, and the patient remained in complete remission with normal blood counts and bone marrow morphology. Auto-UCB transplantation without chemotherapy conditioning can be considered a therapeutic option for children with stored cord blood cells.

[Results of immunosupressive therapy in children with severe aplastic anaemia. Report of the Polish Paediatric Haematology Group].

Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combined immunosuppressive therapy is given. evaluation of results of immunosupressive therapy in children with severe aplastic anaemia. SAA was diagnosed in 105 children (42 girls, 73 boys), aged 2-18 years, in the eleven haematological centres in Poland, between 1993-2007. All patients received the Severe Aplastic Anaemia Working Party of the EBMT protocol which included: antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone. Granulocyto- or granulocytomacrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84 or 112 and 180 of the therapy. complete remission occurred in 53 patients (51.5%), partial remission in 27 (24.7%), no response was obtained in 25 children (23.8%) on day 180, of the therapy. Period of observation was from 12 months to 12.5 years. During this time relapse occurred in 10 patients (9.5%). We observed 22 deaths: 8 early, during the first 3 months of IS and 14 after the first 3 months of immunosuppresive therapy (IS). At present 70 children (66.6%) are in first remission with lasts from 12 months to 12.5 years. The survival at 12.5-years is 78.6%. During the 12.5 years of follow-up we had two cases with a late clonal complication (PNH and MDS). Transformation to acute nonlymphoblastic leukaemia was observed in two of our patients. 1. Immunosuppresive therapy (IS) in children with SAA, without bone marrow family donors, is more effective after introduction of combined IS (12.5 years survival in this study was 80% for children with very severe aplastic anaemia (v SAA). 2. In our studies among the children followed up after IS therapy, there were: 1 case of periodic nocturnal haemoglobinuria (PNH), 1 case of myelodysplastic syndrome (MDS) and 2 cases of myeloid leukaemia (probability of incidence was 3.8%).

First-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared with first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for acquired severe aplastic anemia.

Acquired severe aplastic anemia is a rare and potentially fatal disease, which is characterized by hypocellular bone marrow and pancytopenia. The major signs and symptoms are severe infections, bleeding, and exhaustion. First-line allogeneic hematopoietic stem cell transplantation (HSCT) of a human leukocyte antigen (HLA)-matched sibling donor (MSD) is a treatment for newly diagnosed patients with severe aplastic anemia. First-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin (as first-line immunosuppressive therapy) is an alternative to MSD-HSCT and is indicated for patients where no MSD is found. To evaluate the effectiveness and adverse events of first-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared to first-line immunosuppressive therapy including ciclosporin and/or antithymocyte or antilymphocyte globulin in patients with acquired severe aplastic anemia. We searched the electronic databases MEDLINE (Ovid), EMBASE (Ovid), and The Cochrane Library CENTRAL (Wiley) for published articles from 1946 to 22 April 2013. Further searches included trial registries, reference lists of recent reviews, and author contacts. The following prospective study designs were eligible for inclusion: randomized controlled trials (RCTs) and non-randomized controlled trials if the allocation of patients to treatment groups was consistent with 'Mendelian randomization'. We included participants with newly diagnosed severe aplastic anemia who received MSD-HSCT or immunosuppressive therapy without prior HSCT or immunosuppressive therapy, and with a minimum of five participants per treatment group. We did not apply limits on publication year or languages. Two review authors abstracted the data on study and patient characteristics and assessed the risk of bias independently. We resolved differences by discussion or by appeal to a third review author. The primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, no response to first-line immunosuppressive therapy, graft-versus-host-disease (GVHD), relapse after initial successful treatment, secondary clonal and malignant disease, health-related quality of life, and performance score. We identified three trials that met the inclusion criteria. None of these trials was a RCT. 302 participants are included in this review. The three included studies were prospectively conducted and had features consistent with the principle of 'Mendelian randomization' as defined in the present review. All studies had a high risk of bias due to the study design. All studies were conducted more than 10 years ago and may not be applicable to the standard of care of today. Primary and secondary outcome data showed no statistically significant difference between treatment groups. We present results for first-line allogeneic hematopoietic stem cell transplantation of an HLA-matched sibling donor, which we denote as the MSD-HSCT group, versus first-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin, which we denote as the immunosuppressive therapy group in the following section.The pooled hazard ratio for overall mortality for the MSD-HSCT group versus the immunosuppressive therapy group was 0.95 (95% confidence interval 0.43 to 2.12, P = 0.90, low quality evidence). Therefore, overall mortality was not statistically significantly different between the groups. Treatment-related mortality ranged from 20% to 42% for the MSD-HSCT group and was not reported for the immunosuppressive therapy group (very low quality evidence). The authors reported graft failure from 3% to 16% for the MSD-HSCT group and GVHD from 26% to 51% (both endpoints not applicable for the immunosuppressive therapy group, very low quality evidence). The authors did not report any data on response and relapse for the MSD-HSCT group. For the immunosuppressive therapy group, the studies reported no response from 15% (not time point stated) to 64% (three months) and relapse in one of eight responders after immunosuppressive therapy at 5.5 years (very low quality evidence). The authors reported secondary clonal disease or malignancies for the MSD-HSCT group versus the immunosuppressive therapy group in 1 of 34 versus 0 of 22 patients in one study and in 0 of 28 versus 4 of 86 patients in the other study (low quality evidence). None of the included studies addressed health-related quality of life. The percentage of the evaluated patients with a Karnofsky performance status score in the range of 71% to 100% was 92% in the MSD-HSCT group and 46% in the immunosuppressive therapy group. There are insufficient and biased data that do not allow any conclusions to be made about the comparative effectiveness of first-line allogeneic hematopoietic stem cell transplantation of an HLA-matched sibling donor and first-line treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin (as first-line immunosuppressive therapy). We are unable to make firm recommendations regarding the choice of intervention for treatment of acquired severe aplastic anemia.

Treatment of aplastic anaemia with antilymphocyte globulin and high-dose methylprednisolone.

Twenty-three consecutive adults with bone marrow aplasia who, apart from one individual, lacked a sibling suitable for allogeneic transplantation, received five daily infusions of 50 mg/kg of antilymphocyte globulin (ALG) concurrently with high-dose (500 mg) methylprednisolone (HDMP), followed by oral prednisone at a dose of 30 mg until day 30. One patient died early so that response could not be determined, but data are available and included in the toxicity as well as survival analysis. Haematological response occurred in 13 of the remaining 22 (59%). This followed a single course of treatment in 12, with complete response achieved in five of this group and a second course required in one. At a median follow-up of 20 months (range 5-60), there have been five relapses and 13 patients are alive, including 12 responders who have Karnofsky ratings between 90% and 100%. Of the other nine individuals, only two are alive, with 1 at 12 months still requiring active support and the second, after failing further courses of treatment, at 41 months having a partial response to lymphocytapheresis and plasma exchange. Failure to respond was a significant adverse predictor for survival (P = 0.022). This study involved two distinct batches of ALG, with response occurring in 1/7 (14%) patients treated with the first lot, but in 12/15 (80%) of those individuals who were treated with the second (P = 0.007). Only a pretreatment mean cell volume (MCV) greater than 100 fL predicted for response (P = 0.0088). Confirmation is hereby provided for the efficacy of ALG used in combination with HDMP for treatment of aplastic anaemia, with further support for the observation that not all batches of this product are comparable in bringing about haematologic response in these individuals.

[Treatment of severe acquired aplastic anemia].

Severe acquired aplastic anaemia is associated with high morbidity and mortality despite improvement in the results obtained both with bone marrow transplantation and with immunosuppressive treatment. Early bone marrow transplantation is the treatment of choice for patients under 45 years of age, if the neutrophil granulocyte count is less than 0.2-0.5 x 10(9)/l and an HLA-identical sibling donor is available. Other patients should receive primary immunosuppression with antithymocyte globulin, cyclosporin and glucocorticoid in combination with granulocyte colony-stimulating factor. If they fail to respond after three months, and a donor is available, such patients may be treated with bone marrow transplantation. However, transplantation with marrow from donors other than HLA-identical siblings is still at an experimental stage.

King Fahad Specialist Hospital Dammam

Hemato-oncology: acute leukemias, chronic leukemias, multiple myeloma and other plasma cells disorders, chronic myeloproliferative neoplasms, and lymphomas: Hodgkin and non-Hodgkin types Bone marrow failure syndromes: aplastic anemia, myelodysplastic syndromes and hereditary bone marrow failure syndromes. High dose chemotherapy and stem cells rescue [autologous transplantation] for: myeloma, lymphoma, acute myeloid leukemia] Allogeneic hematopoietic stem cell transplantation (HSCT) for: acute and chronic leukemias, bone marrow failure syndromes and relapsed /refractory Multiple myeloma and Lymphoma Microangiopathic hemolytic anemias Consultation Services for Hemoglobinpathy. Refractory idiopathic thrombocytopenic purpura. Hemolytic anemias. Cytopenias. Thromboembolic disorders and cancer-related thrombosis. Therapy-related thrombocytopenia including Heparin-induced thrombocytopenia.

[Clinical study on haploid HLA-matched hematopoietic stem cell transplantation for treatment of malignant hematological disease].

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective method to treat malignant hematological disease. However the human leukocyte antigen (HLA)-matched sibling donors can be found for only 25%-30% patients. The probability of finding an unrelated matched donor is 1/50000-1/100000, or even lower. If we choose haploid HLA-matched hematopoietic stem cell transplantation instead, we may be able to find donors for 90% patients. Our present study was to explore the feasibility of allo-HSCT by using haploid HLA-matched donor in treatment for malignant hematological disease. Twenty-five patients with malignant hematological disease received allo-HSCT with HLA 2 or 3 antigen mismatched related donors. All patients were treated with intensive immunosuppression, granulocyte colony stimulating factor (G-CSF) mobilization, antithymocyte globulin (ATG) and combination of bone marrow and peripheral blood stem cell transplantation. The conditioning regimen was intensified and prolonged by using the combination of cyclosporine (Cs) A, MMF, ATG and anti-CD25 antibody for graft-versus-host disease (GVHD) prophylaxis. All patients achieved sustained, full donortype engraftment. Acute GVHD occurred in 21 of 25 patients. Eight of them were grade I aGVHD, six grade II aGVHD, two grade III aGVHD and five grade IV aGVHD. The cumulative incidence of grade II-IV aGVHD was 48%,and grade III-IV aGVHD was 28.57%. Chronic GVHD was observed in 12 of 25 patients and none of them developed extensive cGVHD. Sixteen patients were alive and disease free, with 64.0+/- 2.98% 1 year disease-free survival rate. One year overall survival rate was 64.0+/-3.08%. Nine patients died, 1 from relapse and 8 from transplantation related mortality. Haploid HLA-matched allo-HSCT is a relatively efficient method for the treatment of patients with malignant hematological disease, who have no related matched donors. Nevertheless, strict administration should be carried out since it's a high risk approach.

[Reduced intensity of BuCy conditioning regimen for transplantation in the treatment of malignant hematologic diseases].

To evaluate the use of a new reduced intensity of BuCy conditioning regimen for the treatment of malignant hematologic diseases in aged or intolerable patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the siblings. Twelve patients with acute lymphoblastic leukemia (ALL, n = 4), acute myelogenous leukemia (AML-M(2), n = 2), chronic myelogenous leukemia (CML, n = 4), and myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB, n = 2) were intolerant of conventional myeloablative therapy because of age (older than 50 years) or having severe concurrent diseases. The median age was 49 years (range 42-64 years). Seven were males and five females. Two of the 12 patients were HLA one antigen-mismatched and the rest HLA identical with their donors. The low dosage conditioning regimen consisted of busulfan (2 mg.kg(-1).d(-1) for 3 days), Ara-C (2 g.m(-2).d(-1) for 1 or 2 times), cyclophosphamide (1.0 g.m(-2).d(-1) for 2 days) and anti-T-lymphocyte globulin (ATG 2.5 mg.kg(-1).d(-1) for 4 days, -5 - -2 day). Granulocyte colony-stimulating factor mobilized bone marrow and peripheral blood stem cells (PBSC) were harvested (1 patient using PBSC alone). All patients received cyclosporin A, short-term MTX and mycophenolate mofetil (MMF) for prophylaxis of acute graft-versus-host disease (aGVHD). DNA short tandem repeat (STR) sequence analysis, cytogenetics and molecular-biologic technique were used to analyze chimerism. All the patients were well tolerated the regimen, with no severe regimen related toxicity. In all the 12 patients, absolute neutrophil count > or = 0.5 x10(9)/L was achieved in 11 to 17 (median 15) days and platelet count > 20 x 10(9)/L in 10 to 23 (median 15) days after transplantation. Complete chimerism was achieved in 11 patients and 1 patient was in mixed chimerism at one month after HSCT. With a median follow-up of 14.5 (4.0-24.0) months, 7 of the 12 patients (58.0%) were alive and 5 (42.0%) of the 7 were disease-free. The probabilities of OS and DFS at 12 months were 75.0% and 48.1%. Five patients (41.6%) had aGVHD and four had local chronic GVHD with a cumulative probability of chronic GVHD of 41.5%. This reduced intensity conditioning regimen is well tolerated and safe for HSCT in the older patients or patients with severe concurrent medical conditions and can achieve full chimerism and long-term disease-free survival.

Haematopoietic system

Clinical significance Stem cell transplant A stem cell transplant is a transplant intended to replace the progenitor hematopoietic stem cells Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin). It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.

Treatment of severe aplastic anemia with high-dose methylprednisolone and antilymphocyte globulin.

Fifty patients with severe aplastic anemia (SAA) were treated with immunosuppressive regimens consisting of high-dose 6-methylprednisolone (HD-6MPr) followed by or given in combination with anti-lymphocyte globulin (ALG). Eighteen of 50 patients given one course of immunosuppression (IS) showed a response, as defined by self-sustaining peripheral blood counts, with no further need for transfusions; 8 of 27 and 2 of 7 patients given, respectively, two or three courses of IS responded. The overall response rate was 28 of 50 (56%). Seventeen patients died, 5 are alive but pancytopenic. The actuarial six-year survival is currently 65%. The following prognostic factors on admission were significantly associated with response to IS: 1) age over 30 years (P = .005), 2) a short interval from diagnosis to treatment (P = .03), 3) a small number of transfusions before treatment (P = .004). The sex of the patient, the number of transfusions before treatment, and the number of CFU-c from unfractionated as well as from T-depleted bone marrow had no significant influence on response to IS. After one month from IS, however, patients responding to IS had a significantly (P = .01) higher number of CFU-c on T-depleted marrow cells, compared with nonresponders. The present study confirms that over 50% of patients with SAA can be successfully treated with IS. Older patients, with a short interval from diagnosis to treatment and with rapid recovery of CFU-c growth on T-depleted marrow, have the best chance for autologous hematopoietic reconstitution.

Special Education: Aplastic Anemia.

WHAT IS HYPOPLASTIC ANEMIA? Aplastic anemia is a hematological disease characterized by pancytopenia and bone marrow hypoplasia. Acquired cases of aplastic anemia are almost all idiopathic and arise from unknown causes. Other cases of aplastic anemia are secondary and are caused by radiation, chemicals or viruses. PATHOPHYSIOLOGY: Aplastic anemia is manifested as a marked reduction in the number of pluripotent hematopoietic stem cells, but why this occurs is still uncertain. Some of the proposed causes include abnormalities of the hematopoietic stem cells, abnormalities in the hematopoietic microenvironment, and immunologically mediated damage to the hematopoietic stem cells (Figure 1). ABNORMALTIES OF THE HEMATOPOIETIC STEM CELLS: Patients with aplastic anemia, and long-term survivors in particular, are at increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute myelocytic leukemia. This suggests that, in at least some of these patients, the hematopoietic stem cells themselves are abnormal. It also suggests that in some of these patients the blood cells are clonal (that is, all the blood cells are derived from a single pluripotent stem cell). In short, what these findings imply is that aplastic anemia may be caused by the emergence of an abnormal clone. Clonal hematopoiesis, however, can also be considered nothing more than a consequence. In other words, it is possible that hematopoiesis in this kind of patient is performed by a lone pluripotent stem cell that somehow managed to survive eradication. No definitive interpretation of clonal hematopoiesis has been agreed upon, and it is still a topic for future research. ABNORMAL HEMATOPOIETIC MICROENVIRONMENT: The presence of stromal cells, which form the microenvironment of bone marrow, is very important in hematopoiesis. Hematopoietic stem cells proliferate and differentiate either by adhering to stromal cells or by being stimulated by the various hematopoietic factors that stromal cells produce. Therefore, it is quite possible that aplastic anemia is caused by abnormalities in the hematopoietic microenvironment. However, many separate studies have demonstrated that the hematopoietic microenvironment in the vast majority of aplastic anemia cases is normal. IMMUNE MECHANISMS: Immunosuppressive agents are often effective in treating aplastic anemia, and therefore it is believed that immunological mechanisms contribute to the disease in more than half the cases. The following mechanisms have been proposed as causes for the onset of immunologically mediated aplastic anemia: * Decreases in Hematopoietic Factors Produced by Monocytes and Lymphocytes. Some patients with aplastic anemia show decreased production of interleukin 1 (IL-1) by peripheral blood monocytes, and it is possible that a drop in the concentration of this factor is linked to the onset of the disease [1]. It is also possible, however, that decreased IL-1 production by monocytes is not a cause of the disease, but merely a consequence. Moreover, no cases have been reported that exhibit reduced production of hematopoietic factors produced by lymphocytes such as GM-CSF, IL-3, or IL-6. * Damage by Cytokines that Suppress Hematopoiesis. It has been reported that increased levels of interferon &ggr; (IFN-&ggr;), which is produced by lymphocytes, and tumor necrosis factor &agr; (TNF-&agr;), which is produced by monocytes and macrophages, are found in the bone marrow and peripheral blood of aplastic anemia patients [2, 3]. These two factors act as suppressors of hematopoiesis, and it is possible that they contribute to the disease. The increase of these inflammatory cytokines in the bone marrow strongly suggests the presence of either specific or non-specific destruction of the hematopoietic stem cells by immunoregulatory cells. * Suppression of Hematopoiesis by Cytotoxic T Cells (Killer T Cells). Cases have been reported in which cytotoxic T cell clones that damage the autologous hematopoietic precursor cells are present [4]. Therefore, we can easily conceive of a mechanism in which these cytotoxic T cells specifically destroy the hematopoietic stem cells and cause aplastic anemia. * Suppression of Hematopoiesis by Natural Killer (NK) Cells. NK activity of aplastic anemia patients is depressed, and, generally speaking, it is highly unlikely that NK cells contribute to this condition. However, it has been reported that clonal NK cells are thought to cause the disease in patients exhibiting pancytopenia and bone marrow hypoplasia. Therefore, when this disease is diagnosed, a peripheral blood granular lymphocyte count and NK cell surface marker analysis should always be performed. DIAGNOSIS: A necessary condition for the diagnosis of aplastic anemia is the presence of pancytopenia. Moreover, it is necessary to rule out all other causes of pancytopenia. It is especially important in differential diagnosis to look for PNH and MDS. In cases of aplastic anemia there are patients that exhibit PNH during the course of the disease, and this condition is called aplastic anemia-PNH syndrome. It has recently been shown that bone marrow and peripheral blood cells in some patients diagnosed with aplastic anemia are partially lacking GPI anchor proteins (CD16, CD55, and CD59) [5]. Whether such patients become to exhibit aplastic anemia-PNH syndrome in the future remains to be elucidated. In MDS the bone marrow generally exhibits normoplasia or hyperplasia, and only in rare cases does it exhibit hypoplasia. This condition is referred to as hypoplastic MDS. Hypoplastic MDS can be differentiated from aplastic anemia by the presence of abnormal cell morphology that is sometimes accompanied by chromosomal abnormalities. TREATMENT:Aplastic anemia is treated with androgens, high-dose methylprednisolone, cyclosporin A (CyA), antithymocyte globulin (ATG), antilymphocyte globulin (ALG), hematopoietic growth factors such as G-CSF, and bone marrow transplantation. Interestingly, patients who require continuous CyA administration to maintain stable hematopoiesis have a specific HLA class II haplotype (DRB1*1501-DQA1*0102-DQB1*0602) [6]. Recent reports from EBMT SAA Working Party showed the excellent therapeutic result (response rate 82%) when severe cases were treated with ALG, CyA and G-CSF in combination [7].

[A clinical analysis of HLA-identical hematopoietic stem cell transplantation for severe aplastic anemia.].

To study the outcome of HLA-identical hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). Twenty patients diagnosed with SAA received allogeneic HSCT from HLA-identical donors (17 from siblings and 3 from unrelated donors) between January 2000 and November 2008. Conditioning regimen consisted of cyclophosphamide (Cy) and anti-thymocyte immunoglobulin (ATG). The patients were administrated with G-CSF-primed bone marrow(G-BM) and mobilized peripheral blood (G-PB) as grafts from the sibling donors or only G-PB from the unrelated donors. The median infused number of mononuclear cells and CD(34)(+) cells were 7.89 (4 - 14.21) x 10(8)/kg and 2.60 (0.81 - 4.45) x 10(6)/kg. All the patients got engraftment with 100% donor chimerism. The median time of neutrophil and platelet engraftment were 14 (11 - 20) d and 12 (8 - 108) d respectively. The cumulative incidence rate of acute GVHD at 100 d was 16% (grade I: 3 cases, grade II: 3 cases). Chronic GVHD occurred in 7 of the 19 evaluable cases (4 limited, 3 extensive). Till February 28, 2009, with a median follow-up of 18 months, 17 patients were alive and the overall survival rate was 82.5%. The study confirms that using G-PB with or without G-BM as graft after Cy+ATG conditioning results in excellent outcome of HLA-identical HSCT in patients with SAA.

[Immunosupressive therapy of aplastic anemia patients: successes and failures (single center experiment 2007-2016)].

Treatment programs for patients with acquired aplastic anemia include two main therapeutic options: allogeneic bone marrow transplantation and combined immunosuppressive therapy (IST). However, combined IST remains the method of choice for most adult AA patients. This study included 120 AA patients who received IST at the National Research Center for Hematology in 20072016. The analysis was applied to 120 patients. Median age was 25 (1765) years, M/F: 66/54, SAA/NSAA: 66%/34%. Effectiveness of IST was carried out in 120 patients with AA. This group did not include 8 SAA patients who died during the first 3 months from the start of treatment from severe infectious complications (early deaths 6.2%) and 2 AA patients who dropped out of surveillance. The observation time was 55 (6120) months. Paroxysmal nocturnal hemoglobinuria (PNH clone) was detected in 67% of AA patients. The median PNH clone size (granulocytes) was 2.5 (0.0199.5)%. The treatment was according to the classical protocol of combined IST: horse antithymocytic globulin and cyclosporin A. Most of patients (87%) responded to combined immunosuppressive therapy. To achieve a positive response, it was sufficient to conduct one course of ATG to 64% of patients, two courses of ATG 24% of patients and 2% of patients responded only after the third course of ATG. A positive response after the first course was obtained in 64% of patients included in the analysis. Most of the responding patients (93%) achieve a positive response after 36 months from the start of treatment. Therefore, the 3rd6th months after the first course of ATG in the absence of an answer to the first line of therapy can be considered the optimal time for the second course of ATG. This tactic allows to get an answer in another 58% of patients who did not respond to the first course of ATG. The probability of an overall 10-year survival rate was 90% (95% confidence interval 83.696.2).