In this group of patients, the aim of treatment cannot be merely palliative.For all these reasons, the number of stem cell transplants performed in individuals with CLL is increasing,45 the hope being that – as with other hematological malignancies – transplants can cure a fraction of patients.
A two-step acquisition strategy was employed, starting with the acquisition of 10 was achieved in all cases after performing dilutional experiments using samples from seven CLL patients.With a median follow-up of 26.5 months (range, 12–52), four of the five MRD( ) patients relapsed at 9, 15, 17 and 18 months after transplant, respectively.In contrast, only two patients of the nine MRD(−) patients have relapsed at 15 and 38 months (P = 0.02), and four became MRD( ) at 6, 12, 30, and 42 months after transplantation, respectively.MRD was simultaneously detectable by both methods (ie immunophenotypic and molecular biology) in all cases.The results of PCR analysis in the leukapheresis product were totally consistent with those in bone marrow and peripheral blood pre-mobilization in all patients.Of the 12 patients that were allografted, three (25%) died in the early post-transplant period, one had resistant disease, and eight (67%) achieved CR.
Among the latter, no evidence of MRD post-transplantation was observed in five cases, while a delayed clearance of MRD (up to 22 months after transplantation) was seen in two, and a persistent positivity of MRD after transplant was detectable in another patient until last follow-up (12 months).
One patient (UPN 6) was transplanted after having attained MRD(−) CR.
In another patient who achieved a clinical CR pre-transplant (UPN 23), a residual CLL population was detected by flow cytometry and PCR analyses.
Twenty-six individuals diagnosed with CLL according to the National Cancer Institute-Sponsored Working Group criteria (NCI/WG)6 undergoing stem cell transplantation (14 autologous, 12 allogeneic) in our institution since 1991 are the subject of the present analysis.
Patients up to the age of 60 were offered transplantation if they had active disease with any of the following poor prognostic features: advanced clinical stage (Binet's B or C), rapid doubling time (Immunophenotypic analysis of lymphoid population and molecular studies of the rearrangement pattern of the CDRIII region of the heavy chain immunoglobulin (Ig H) were performed at the time of diagnosis and/or before treatment.
DNA was extracted from PB and BM samples using a sodium chloride extraction method.14 The rearrangement pattern of Ig H was analyzed by means of Southern blot method and PCR of the third complementary region (CDRIII) of the Ig H gene.