Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation

Abstract

AA who developed MDS or AML following IST reported a 5-year event-free survival of 41%. 13 However, there no large-scale study of transplantation for post-AA MDS has been made, and there are no data comparing results to patients with de novo MDS. Thus, in the present study, we analyzed transplant outcomes of post-AA MDS patients, carried out a matched-pair analysis including patients with de novo MDS, and determined prognostic factors for transplant outcome. Methods Study populationIn the databases of the Center for International Bone Marrow Transplantation Research (CIBMTR) and the Fred Hutchinson Cancer Research Center, we identified 123 patients transplanted from 1991 through 2011 for MDS developing after treatment of aplastic anemia with IST (post-AA MDS). Cases of marrow failure/AA possibly associated with constitutional/inherited disorders were excluded. The time interval from the diagnosis of AA to the establishment of the diagnosis of MDS was 4-491 months (median 34 months). The MDS categories comprised refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with excess blasts (RAEB), and refractory anemia with excess blasts in transformation (RAEB-t). The data bases did not allow for categorization according to the WHO classification, nor was it possible in this retrospective analysis to categorize patients according to the recently proposed five cytogenetic risk groups as used in the revised International Prognostic Scoring System (IPSS-R).14 Patients with AML (>30% marrow myeloblasts) and CMML were excluded. We conducted a matched pair analysis, matching cases to control on factors shown to influence transplantation outcomes. Overall, 1473 patients with de novo MDS were reported to the CIBMTR during the study period. Patients with MDS related to cytotoxic therapy, Fanconi anemia and other inherited marrow failure syndromes were excluded from the study. Cases were matched to controls from this cohort for age (< 10 years vs. ≥ 10 years), disease status at transplantation (RA/RARS vs. RAEB/RAEB-t), donor type (HLA-identical sibling vs. other relative vs. matched unrelated donor vs. mismatched unrelated donor), year of transplant (1991-1999 vs. 2000-2011), and conditioning regimen intensity (myeloablative vs. reduced intensity). Cases and controls were matched to their respective age as close as possible: the difference in age of cases and controls was 0-1 year for 56%, 2-5 years for 30%, and 6-10 years for the remaining 14%. For this latter sub-group, the median age for cases was 23 years, compared to 29 years for controls. DefinitionsCytogenetic risk was graded into good, intermediate, and poor, based on the IPSS.14 Time of engraftment was defined as the first of three consecutive days with neutrophil counts that exceeded 0.5 x10 9 /L. Acute and chronic graft-versus-host disease (GvHD) were defined and graded according to standard criteria. 15,16 Overall survival (OS) was defined as survival irrespective of disease status, and relapse-free survival (RFS) as sur...

How I treat acquired aplastic anemia

“…85 The most worrisome problem is cytogenetic evolution or a myelodysplastic syndrome, which has been reported to occur in 18% of patients 86 and calls for a transplant strategy for eligible patents. 87 For this reason, morphologic and cytogenetic examination of marrow cells should be performed in patients with SAA after immunosuppressive treatment, possibly at yearly intervals.…”

Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

“…Though SAA is not considered overtly malignant, it confers significant risk to the patient because of its late complications, which include relapse and secondary clonal disease [5–8]. Infection (usually fungal) is the most common cause of early death; however, hemorrhage, clonal disease (myelodysplastic syndromes [MDS] [9], leukemia, and paroxysmal nocturnal hemoglobinuria [PNH]), and transfusional iron overload are other causes of severe morbidity and mortality [10]. Improved supportive care has led to significant progress in controlling the acute aspects of the disease over the past 2 decades, but little progress has been made controlling the late complications of SAA, especially the risk for relapse and secondary clonal disorders.…”

Myelodysplastic syndrome/acute myeloid leukemia evolving from aplastic anemia: Efficacy of hematopoietic stem cell transplantation

“…of conditioning regimen also did not have significant impact on the HSCT results, but some studies declare benefits of myeloablative conditioning for treatment of secondary MDS [21,23]. In our study, only 3 out of 16 patients were subjected to myeloablative conditioning, with engraftment in 2 of 3 cases.…”