Treatment of High Risk AML and MDS with Ara-C-Containing Standard Chemotherapy Followed by Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (RIC-SCT) during Aplasia: A Survey of the German Cooperative Transplant Study Group (GCTSG).

Abstract

Prognosis of patients (pts.) with refractory or relapsed acute myeloid leukaemia (AML) or advanced myelodysplasia (MDS) is poor. Preliminary reports suggest that induction of aplasia by a standard AML regimen followed by reduced intensity conditioned stem cell transplantation (RIC-SCT) in aplasia may be an effective strategy in this situation. A survey was conducted by the German Cooperative Transplant Study Group (GCTSG) to investigate the outcome after such an approach. In April 2006, GCTSG centers were asked if they had performed RIC-SCT in aplasia. Centers with positive response received a questionnaire including details on patient and donor characteristics, disease status, induction chemotherapy, transplant procedure and outcome.Data on 44 pts. (24 male, 20 female; median age 49y, range 19 – 66) with high-risk MDS (n=9), relapsed (n=16) or primary refractory AML (n=19) were reported by 3 centers. Pts. received aplasia-inducing chemotherapy with the following regimens: idarubicine / fludarabine / ara-C (n=16), daunorubicine / ara-C (n=15), fludarabine / ara-C / amsacrine (n=5), or other ara-C-based schedules (n=8). Subsequent transplant conditioning therapy consisted of melphalan (150 mg/m2) plus fludarabine (150mg/m2) in n=28, TBI (total body irradiation, 8Gy) plus fludarabine (150mg/m2) in n=11, and TBI (4Gy) plus cyclophosphamide (80 – 120 mg/kg) in n=5 pts. and was commenced after a median of 15 days (8 – 40) from the start of the preceding chemotherapy. Allogeneic peripheral blood (n=41) or bone marrow (n=3) stem cells from sibling (n=16), matched unrelated donors (n=18) or mismatched donors (n=10) were infused thereafter. Graft versus host disease (GVHD) prophylaxis was performed with cyclosporin A monotherapy (n=33) or by combination of a calcineurine inhibitor and methotrexate (n=11), n=31 received additional anti-thymocyte globuline.43 pts. achieved stable engraftment and 41 showed > 90% donor chimerism after 28 – 90 days. Grade 2–3 acute GVHD occurred in 34%, whereas limited or extensive chronic GVHD was seen in 26% of the evaluable pts. The 100-day mortality rate was 24%: 5 pts. succumbed to treatment related complications, 4 to disease relapse. The median follow up is 183 days (19–1453). Actuarial survival rates estimated by Kaplan-Meier analysis are 56% and 30% at 6 and 12 months, whilst actuarial progression free survival rates are 42% and 30% at 6 and 12 months, respectively.This multi-center retrospective analysis suggests feasibility of the approach combining leukemia burden reduction by standard AML induction chemotherapy followed by RIC-SCT performed in aplasia. Treatment-related complications were comparable to those of a conventional transplant setting, thus disease control was achievable in a substantial proportion of patients with poor prognosis AML and MDS. Prospective studies are needed to assess whether durable remissions are achievable in patients with these otherwise fatal conditions.