Immunosuppressive regimens that effectively prevent graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) have been associated with an increased incidence of posttransplantation lymphoproliferative disorder (PTLD) in the first year after transplantation. We evaluated the incidence of PTLD associated with the use of high-dose, posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis. From 2000-2011, 785 adult alloBMT patients received PTCy as GVHD prophylaxis at the Johns Hopkins Hospital, including 313 who received PTCy as sole GVHD prophylaxis. HLA-haploidentical or unrelated donor grafts were used for 526 (67%) patients. There were no cases of PTLD in the first year after alloBMT. PTLD is rare after alloBMT using PTCy, even in high-risk alternative donor transplants.
Post-transplant cyclophosphamide (PTCy) can be used for graft versus host disease (GVHD) prophylaxis alone or in combination with other agents and is associated with excellent rates of engraftment, acute and chronic GVHD, and an absence of post-transplant lymphoproliferative disease. No study has previously evaluated the risk for developing donor derived malignancy (DDM) in patients who receive PTCy. Giving chemotherapy in the immediate post-transplant period carries with it a theoretic risk of disturbing the graft at a time of increased hematopoietic stress and causing or accelerating the development of malignancy. From 2000-2011, 789 patients underwent allogeneic transplant and received PTCy at the Johns Hopkins Hospital. There were four cases of DDM identified among this large population, which is similar to or below the rate of DDM published in the literature. We found that the estimated cumulative incidence by competing risk analysis of DDM is 1.4% (standard error=1.02%). The use of PTCy does not appear to increase the risk of DDM.
Data on adults included 644 (598 allo + 46 auto) evaluable patients out of total 835 patients reported. In pediatric cohort 165 patients suffered from malignancies, 356 patients were transplanted for non-malignant diseases; 437 underwent a first SCT, 87 had a subsequent transplant. In adult group 626 were treated for hematological malignancies and 18 for nonmalignant diseases (SAA or thalassemia). No data on auto-SCT in adults were published after 2004. The majority of pediatric patients received treosulfan in dose 39-45 mg/m2 (332 patients, 62%). Most of adult patients treated after 2007 received dose of 42 mg/m2. Results: The main indications for treosulfan use in pediatric population were non-malignant diseases (68%) or second SCT, while among adults older age (>50 years) and/or comorbidities disqualifying from myeloablative conditioning. No correlation between the given treosulfan dose and the grade III/IV toxicity was observed both in children and in adults. No association between dose and GVHD, OS, DFS, relapse incidence and TRM was found both in children and in adults. Conclusions: Treosulfan-based conditioning with its low toxicity profile and dose-dependent myelotoxicity is a good option in children treated with non-malignant diseases. Additionally, both children and adults not eligible for conventional transplant regimen can be offered this treatment with acceptable results. Toxicity and survival were similar in children and adults, while acute and chronic GVHD incidence were higher in adult population.
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