Outcome of Adult Severe or Very Severe Aplastic Anemia Treated with Immunosuppressive Therapy Compared with Bone Marrow Transplantation: Multicenter Trial

2003 ◽  
Vol 78 (2) ◽  
pp. 133-138 ◽  
Author(s):  
Myung-Ju Ahn ◽  
Jung-Hye Choi ◽  
Young-Yeul Lee ◽  
Il-Young Choi ◽  
In-Soon Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Marrow Transplantation ◽  
Multicenter Trial ◽  
Severe Aplastic Anemia

Antithymocyte Immunoglobulin in Severe Aplastic Anemia and Bone Marrow Transplantation

1996 ◽  
Vol 30 (10) ◽  
pp. 1164-1174 ◽  
Author(s):  
Christine Colby ◽  
Cheryl A. Stoukides ◽  
Thomas R. Spitzer
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Intensive Immunosuppressive Therapy

OBJECTIVE: To review antithymocyte immunoglobulin (ATG) and its current role in the treatment of severe aplastic anemia (SAA), focusing on ATG in immunosuppressive therapy compared with bone marrow transplantation (BMT). DATA SOURCES: A MEDLINE search (1966 to 1996) of English-language literature and human subjects pertaining to ATG and BMT therapy in SAA was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-mediated destruction of stem cells. ATG is a potent immunosuppressive agent and has emerged as an important therapy for patients with SAA. The exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses resulting in inhibition or altered T-cell function. Numerous trials have evaluated the use of ATG both as monotherapy and in combination with other immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40–70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the optimal immunosuppressive treatment. Questions still remain concerning complications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the survival curve was not achieved. BMT is a potential treatment for SAA. Although there is a high initial mortality due to treatment-related toxicities, successful marrow engraftment provides a cure for SAA. Many patients (75–90%) experience long-term survival after allogenic BMT. Age, donor availability, and severity of disease limit the number of eligible patients. CONCLUSIONS: Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patients who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better understand the pathogenesis of SAA and prevent treatment-related complications is essential to provide the best care to all patients.

scholarly journals Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 491-494 ◽  
Author(s):  
RA Brodsky ◽  
LL Sensenbrenner ◽  
RJ Jones
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
High Dose ◽  
Allogeneic Bone

Severe aplastic anemia (SAA) can be successfully treated with allogeneic bone marrow transplantation (BMT) or immunosuppressive therapy. However, the majority of patients with SAA are not eligible for BMT because they lack an HLA-identical sibling. Conventional immunosuppressive therapy also has major limitations; many of its remissions are incomplete and relapse or secondary clonal disease is common. Cyclophosphamide is a potent immunosuppressive agent that is used in all BMT conditioning regimens for patients with SAA. Preliminary evidence suggested that high-dose cyclophosphamide, even without BMT, may be beneficial to patients with SAA. Therefore, 10 patients with SAA and lacking an HLA-identical sibling were treated with high-dose cyclophosphamide (45 mg/kg/d) for 4 consecutive days with or without cyclosporine. A complete response (hemoglobin level, > 13 g/dL; absolute neutrophil count, > 1.5 x 10(9)/L, and platelet count > 125 x 10(9)/L) was achieved in 7 of the 10 patients. One of the complete responders died from the acquired immunodeficiency syndrome 44 months after treatment with high-dose cyclophosphamide. The 6 remaining patients are alive and in continuous complete remission, with a median follow-up of 10.8 years (range, 7.3 to 17.8 years). The median time to last platelet transfusion and time to 0.5 x 10(9) neutrophils/L were 85 and 95 days, respectively. None of the complete responders has relapsed or developed a clonal disease. These results suggest that high-dose cyclophosphamide, even without BMT, may be more effective than conventional immunosuppressive therapy in restoring normal hematopoiesis and preventing relapse or secondary clonal disorders. Hence, further studies confirming the efficacy of this approach in SAA are indicated.

Non-Myeloablative Conditioning Regimen (NMCR) for Allogeneic Bone Marrow Transplantation (BMT) in Patients with Severe Aplastic Anemia (SAA).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4943-4943
Author(s):  
Joseph Rosenthal ◽  
Anna Pawlowska ◽  
Ellen Bolotin ◽  
Peter Falk ◽  
Cheryl Oliver ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Allogeneic Bone ◽  
Post Transplant

Abstract Allogeneic bone marrow transplantation is a curative form of therapy for patients (pts) with acquired severe aplastic anemia. Current preparative therapies are associated with early and late sequelae such as organ injury, and secondary tumors. Recent studies showed that BMT following reduced-intensity or NMCR may result in long-term survival for a fraction of pts with hematologic malignancies (Giralt, Biol. Blood Marrow Transplant, 13:884, 2007). However, with the exception of BMT for pts With Fanconi’s anemia, little is known about using NMCR for patients with non-malignant disorders. We report the use of NMCR in patients with SAA. Patients and Methods: Four female pts ages 6–12 years, diagnosed with SAA, had allogeneic BMT from an HLA-identical sibling (SIB) (Pts #1 and #2) or a matched unrelated donor (MUD) (pts #3 and #4). The reasons to offer NMCR were: delay in results of chromosome fragility studies (Pt #1), abnormal pulmonary function (Pt #2), history of recent life threatening infection (Pt #3), and failure to respond to immunosuppressive therapy (Pt #4). The NMCR consisted of fludarabine (FLU) (30 mg/m2 x 4), low dose cyclophosphamide (LDC) (5 mg/kg x 4) and rabbit antithymocyte globulin (rATG) (1.5 mg/kg x 4) in patients with SIB donor and FLU, LDC, at a higher dose of 15 mg/kg x 4), rATG and a single fraction of total body irradiation at 200 cGy in patients with a MUD donor. Supportive care, prophylactic anti-microbial therapy, and treatment for prevention of aGvHD were given according to the institution standard guidelines. Results: The NMCR was well tolerated in all 4 patients. Pts #1 and #2 who had a SIB BMT had no transplant-related toxicities, including mucositis or alopecia. Toxicities in the MUD BMT patients included mild mucositis and partial alpecia in both pts. Pt#3 had reactivation od Enterobacter cloacae sepsis with typhlitis and later CMV viremia. Myeloid and platelet engraftment were uneventful in pts #1, #2, and #4. The recovery of peripheral blood counts was slow in Pt #3 following typhlitis and CMV viremia. Myeloid engraftment occurred on day +19 (range 15–33 days). The median time to a platelet count >20,000 unsupported by transfusion was day +33, (range 12–76 days). Periodic engraftmen anlyses using short tandem repeat (STR) by PCRT continue to show full donor chimerism in all 4 pts. There were no signs for acute or chronic graft-vs-host disease (aGvHD or chGvHD, respectively) in pts with SIB BMT. Both patients continue to do well with a fully recovered hematopoietic system 17 months and 42 months post transplant. There were no aGVHD.or chGVHD in Pt#3. Pt #4 had aGVHD of the skin, clinical grade II, which responded well to immunosuppressive therapy. Both MUD BMT pts are well 5 and 3 months post-transplant, respectively, with partial hematopoietic recovery in Pt #3 and normal counts in Pt #4. Conclusion: This data suggests that a non-myeloablative, immunosuppressive regimen is sufficient to provide a stable engraftment in the patients with SAA. This approach may be associated with decreased transplant-related, short- and long-term, toxicities. A larger study is needed to fully evaluate the outcome and the toxicity associated with this conditioning.

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