Is it time for a change? The case for early application of unrelated allo-SCT for severe aplastic anemia

Meyers, Gabrielle; Maziarz, Richard T.

doi:10.1038/bmt.2010.134

Cited by 14 publications

(15 citation statements)

References 44 publications

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“…17,18 Patients who received transplantations within 12 months of diagnosis had a more favorable 2-year OS (96% vs 76%, P ϭ .07). In conclusion, the use of alemtuzumab in SCT for acquired AA is the first reported change in conditioning regimen to result in a major reduction in chronic GVHD compared with previously reported studies.…”

Section: Discussionmentioning

confidence: 99%

“…16 UD HSCT is now considered after failing 1 course of IST. [17][18] Improved outcomes are likely because of improved HLA-matching techniques, better supportive care, and improved conditioning regimens. For example, the use of fludarabine, low-dose CY, and ATG (FCATG) conditioning regimen for young patients, and FCATG with low-dose (2 Gy) total body irradiation (TBI) for older patients, results in 75% and 79% overall survival (OS) at 5 years, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia

Marsh

Gupta

Lim

et al. 2011

Blood

147

130

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We evaluated a novel alemtuzumab-based conditioning regimen in HSCT for acquired severe aplastic anemia (SAA). In a multicenter retrospective study, 50 patients received transplants from matched sibling donors (MSD; n ‫؍‬ 21) and unrelated donors (UD; n ‫؍‬ 29), using fludarabine 30 mg/m 2 for 4 days, cyclophosphamide 300 mg/m 2 for 4 days, and alemtuzumab median total dose of 60 mg (range:40-100 mg). Median age was 35 years (range 8-62). Overall survival at 2 years was 95% ؎ 5% for MSD and 83% for UD HSCT (p 0.34). Cumulative incidence of graft failure was 9.5% for MSD and 14.5% for UD HSCT. Full-donor chimerism (FDC) in unfractionated peripheral blood was 42%; no patient achieved CD3 FDC. Acute GVHD was observed in only 13.5% patients (all grade I-II) and only 2 patients (4%) developed chronic GVHD. A low incidence of viral infections was seen. Factors influencing overall survival were HSCT comorbidity 2-year index (92% with score 0-1 vs 42% with score > 2, P < .001) and age (92% for age < 50 years vs 71% > 50 years, P < .001). Our data suggest that the use of an alemtuzumabbased HSCT regimen for SAA results in durable engraftment with a low incidence of chronic GVHD. (Blood. 2011;118(8): 2351-2357) IntroductionAllogeneic HSCT offers the chance of long-term cure for patients with severe aplastic anemia (SAA), 1-5 but chronic GVHD represents a current major challenge that impacts on quality of life as well as survival. 6 The ideal conditioning regimen for SAA is one that results in sustained engraftment, minimal regimen-related toxicity, and absence of both acute and chronic GVHD. There is no advantage for any degree of chronic GVHD in AA, in contrast to the beneficial impact of GVL effect on HSCT for myeloid malignancies.Over the past few decades, survival after HSCT for acquired SAA has improved greatly. HLA-matched sibling donor (MSD) HSCT results in long-term survival in at least 80% of patients. 1,2,4,5,7,8 The standard of care conditioning for young patients undergoing MSD BM transplantation (BMT) for AA is high-dose cyclophosphamide (CY) 200 mg/kg and ATG, with cyclosporin (CSA) and methotrexate (MTX) as post-graft immunosuppression. Long-term survival occurs in 80%-90% of patients, although this is age-dependent, with only 50% survival above the age of 40-50 years. 3,9,10 Graft rejection occurs in 5%-10%, and acute GVHD in 12%-30%. Notably, chronic GVHD remains a major problem for 30%-40% of patients. In addition, incremental impact of increasing age is observed on the cumulative incidence of acute and chronic GVHD. 3 Unrelated donor (UD) HSCT had previously been reserved for those patients who fail to respond to 2 courses of immunosuppressive therapy (IST), but outcomes after UD HSCT have improved significantly during the past decade. 11-15 A prospective pediatric study from Japan comparing repeat course of IST with UD HSCT showed benefit in favor of early UD HSCT in AA. 16 UD HSCT is now considered after failing 1 course of IST. [17][18] Improved outcomes are likely because of improved HLA-matching ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia

Marsh

Gupta

Lim

et al. 2011

Blood

147

130

View full text Add to dashboard Cite

show abstract

“…6 However, this decision is based on the results of comparative studies of these two therapies mainly conducted in the 1980s, and the outcome of both BMT and IST has dramatically improved over the past three decades. 7,8 Therefore, updated evidences for treatment decision of pediatric SAA are required. We compared the outcome of children with SAA who received IST enrolled in the prospective multicenter trials of IST conducted by the Japan Childhood Aplastic Anemia Study Group 9,10 or BMT from an MFD registered to the Transplant Registry Unified Management Program conducted by the Japan Society for Hematopoietic Cell Transplantation.…”

Section: First Line Treatment For Severe Aplastic Anemia In Childrenmentioning

confidence: 99%

Treatment of acquired aplastic anemia in children

Kojima

2012

Hematology

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“…[2][3][4] Owing to the improved outcome of allogeneic HCT with unrelated donors, it is considered if this treatment should be given an increased role in the future treatment of children and young adults with SAA and no available HLA-identical sibling donor.…”

mentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for severe aplastic anemia: similar long-term overall survival after transplantation with related donors compared to unrelated donors

Mortensen¹,

Jacobsen²,

Heilmann

et al. 2015

Bone Marrow Transplant

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Is it time for a change? The case for early application of unrelated allo-SCT for severe aplastic anemia

Cited by 14 publications

References 44 publications

Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia

Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia

Treatment of acquired aplastic anemia in children

Allogeneic hematopoietic cell transplantation for severe aplastic anemia: similar long-term overall survival after transplantation with related donors compared to unrelated donors

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