Molecular remissions in chronic lymphocytic leukemia after hematopoietic stem cell transplantation.

J Esteve, N Villamor, D Colomer, F Bosch, A López-Guillermo, M Rovira, A Urbano-Ispizua, J Sierra, E Carreras, E Montserrat

Abstract: 

Stem-cell transplant (SCT) is increasingly performed in younger patients with chronic lymphocytic leukemia (CLL) and adverse prognostic factors. Twelve patients (7 males; median age: 47 years, range: 29-51) with high-risk CLL (e.g., advanced stage, diffuse bone marrow involvement, rapid doubling time) have undergone allo-SCT (n = 7) and auto-SCT (n = 5) in our institution since 1991. The source of hematopoietic stem cells was bone marrow in 5 allo-SCT and peripheral blood in the remaining cases (allo-SCT, 2; auto-SCT, 5). Conditioning regimen consisted of cyclophosphamide (120 mg/kg in two consecutive days) and total body irradiation (13 Gy in 7 cases and 12 Gy in 4 patients), and BEAC (BCNU 300 mg/m2 x 1, etoposide 400 mg/m2 x 4, cytarabine 200 mg/m2 x 4, cyclophosphamide 1400 mg/m2 in the remaining one). A T-cell depleted inoculum was used in four cases with an increased GVHD risk (counterflow elutriation of bone marrow, 2; positive selection of CD34+ from leukapheresis blood product, 2). Minimal residual disease (MRD) was assessed by cytofluorometry of lymphoid cells and PCR of the third complementary region (CDR3) of the immunoglobulin heavy chain locus. All patients had been treated before transplantation (median number of treatment lines, 2; range: 1-5); one patient received an allograft after having relapsed from an auto-SCT. Interval from diagnosis to transplant ranged from 12 to 94 months with a median of 41. At transplant, one patient was in molecular CR, eight patients in PR and three patients had a refractory disease. All 11 evaluable patient engrafted. Two patients allografted died due to a treatment related-cause (diffuse alveolar hemorrhage, 1; pulmonary aspergillosis, 1); three patients developed acute GVHD (grade II-IV, 2). No transplant related mortality was observed among autografted patients. After transplantation, ten of 11 patients (91%) evaluable for response achieve CR which was molecular in nine (81%). One patient in clinico-hematological CR but with persistent MRD relapsed at 9 months after transplantation and died afterwards due to disease progression. Seven patients, including 2 refractory to treatment before transplant, remain in molecular CR for a median of 16 months (range, 1 to 58). With the limitation of a small series, estimated actuarial survival and DFS at two years is 81% (95% CI: 43-100%) and 71% (95% CI: 43-99%), respectively. Relapse risk at two years is 12.5% (95% CI: 0-35.5%). In conclusion, a significant proportion of patients with high-risk CLL can achieve long-lasting molecular CR after SCT. The role of transplants in the management of younger patients with high-risk CLL deserves investigation in randomized, controlled trials.
1997

abstract No: 

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Full conference title: 

39th meeting of the American Society for Haemotology
    • ASH 39th (1998)