Fifteen-Year Follow up of Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndromes Using Busulfan-Based Regimens.
Authors: Atallah Ehab , Uberti Joseph , Ayash Lois , Bentley Gail , VanDahm Jennifer , Ratanatharathorn Voravit 
Published: October 2019

We report here the long-term outcome of 95 patients with myelodysplastic syndromes (MDS) who underwent allogeneic stem cell transplantation (SCT) following busulfan-containing regimens. The median age was 43 (range:3–62) and 55 patients were male. Eighty-four patients had primary MDS, 11 had secondary MDS. Twenty patients received induction therapy for leukemic transformation prior to SCT. Pre-transplantation cytogenetic studies were available in 82 patients, and were categorized according to the international prognostic scoring system (IPSS) karyotype groups. The bone marrow biopsies/aspirates were reviewed and classified according to WHO classification (Table 1). Sixty one patients received related donor transplant (54 patients were 6/6 HLA-matched), and 34 patients received unrelated donor transplant (26 patients were 6/6 HLA-matched). Ninty patients received consecutive administration of busulfan 4 mg/kg/day orally for 4 days, cytosine arabinoside 2 g/m2 IV every 12 hours for 4 doses, and cyclophosphamide 60 mg/kg IV daily for 2 days (BAC); and 5 received other busulfan-containing regimens. GHVD prophylaxes were either cyclosporine (75 patients) or tacrolimus (12 patients) regimens, and 8 patients received other regimens. The median duration of transplant hospitalization was 34 days (range:13–121 days). Grade I–IV regimen-related toxicities (RRT) included GI (diarrhea, 32; stomatitis, 38), liver (28), cardiac (19), kidney (15), lung (25), neurological (7) and skin (5). Acute and chronic GHVD occurred in 48 (50%) and 21 (22%) patients, respectively. With a median follow up of survivors of 6.7 years, the Kaplan-Meier estimates for overall survival were 45%±5% (±SE), 35%±6% and 34%±6% at five, ten and fifteen years, respectively (Figure 1). Fifty-four patients died. The causes of death were GHVD (14 patients), relapse (12), infection (11), pulmonary toxicity (3), multiorgan failure (3), hepatic (2), renal (1), cardiac (1) and other causes (7). Non-relapse mortality at 100 days and three years was 22% and 40% respectively. The long-term follow up of patients receiving high-dose busulfan-based regimens for allogeneic SCT in this study indicated durable overall survival with acceptable toxicity.

Patient Characteristics BAC: Busulfan/Ara-C/Cyclophosphamide, BU: Busulfan, CY: Cyclophosphamide, TLI: Total lymphoid irradiation, FLU: Fludarabine, ATG: Antithymocyte globulin, CS: Cyclosporin # of Patients 95 Median Age (range) 43 (3–62) Male/Female 55/40 Cytogenetic risk (IPSS)     Good/Intermediate/Poor 38/14/30     Not available 13 Disease Duration Median (range) 182 (40–1944) Etiology     Denovo/Secondary 84/11 Donor     HLA-identical sibling 54     HLA-nonidentical sibling 7     Unrelated HLA-identical 26     Unrelated HLA-nonidentical 6 WHO Classification     RA 5     RARS 2     RAEB-1 4     RAEB-2 16     RCMD 14     CMML 4     AML 20     MDS-U 6     Not available 24 Source of stem cells     BM/PBSC 69/26 GVHD prophylaxis     CSA/Methylprednisolone 32     CSA/Methotrexate 43     Tacrolimus/Mycelophenolate 7     Tacrolimus/Methotrexate 5 Busulfan regimen     BAC 90     BU/ATG/CS/TLI 2     BU/CY 1     BU/FLU/TLI 2 Figure Figure