Literature DB >> 16278397

Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-).

Dolores Caballero1, Jose A García-Marco, Rodrigo Martino, Victoria Mateos, José M Ribera, José Sarrá, Angel León, Guillermo Sanz, Javier de la Serna, Rafael Cabrera, Marcos González, Jorge Sierra, Jesús San Miguel.   

Abstract

PURPOSE: To evaluate the efficacy of reduced intensity conditioning (RIC) allogeneic transplant in 30 patients with poor-prognosis chronic lymphocytic leukemia (CLL) and/or high-risk molecular/cytogenetic characteristics. EXPERIMENTAL
DESIGN: Eighty-three percent of patients had active disease at the moment of transplant. That is, 14 of the 23 patients analyzed (60%) had unmutated immunoglobulin variable heavy-chain gene (IgV(H)) status; 8 of 25 patients (32%) had 11q-, with four of them also displaying unmutated IgV(H); and six (24%) had 17p- (five were also unmutated).
RESULTS: After a median follow-up of 47.3 months, all 22 patients alive are disease free; overall survival and event-free survival (EFS) at 6 years were 70% and 72%, respectively. According to molecular/cytogenetic characteristics, overall survival and EFS for unmutated CLL and/or with 11q- aberration (n = 13) were 90% and 92%, respectively, not significantly different to those with normal in situ hybridization, 13q- and +12, or mutated CLL (n = 7). All six patients with 17p deletion were transplanted with active disease, including three with refractory disease; all except one reached complete remission after the transplant and two are alive and disease free. Nonrelapse mortality (NRM) was 20%; more than two lines before transplant is an independent prognostic factor for NRM (P = 0,02), EFS (P = 0.02), and overall survival (P = 0.01). Patients older than 55 years have a higher risk of NRM (hazard ratio, 12.8; 95% confidence interval, 1.5-111). Minimal residual disease was monitored by multiparametric flow cytometry in 21 patients. Clearance of CD79/CD5/CD19/CD23 cells in bone marrow was achieved in 68% and 94% of the patients at days 100 and 360, respectively.
CONCLUSION: According to these results, RIC allogeneic transplant could overcome the adverse prognosis of patients with unmutated CLL as well as those with 11q- or 17p-.

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Year:  2005        PMID: 16278397     DOI: 10.1158/1078-0432.CCR-05-0941

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN: 1078-0432            Impact factor:   12.531


  23 in total

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Authors:  Andy C Rawstron; Peter Hillmen
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Review 4.  Clinical application of array-based comparative genomic hybridization for the identification of prognostically important genetic alterations in chronic lymphocytic leukemia.

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5.  Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

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Review 6.  Immunotherapy for chronic lymphocytic leukemia in the era of BTK inhibitors.

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7.  Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome.

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8.  Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia.

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9.  Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines.

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10.  Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

Authors:  Mohamed L Sorror; Barry E Storer; Brenda M Sandmaier; Michael Maris; Judith Shizuru; Richard Maziarz; Edward Agura; Thomas R Chauncey; Michael A Pulsipher; Peter A McSweeney; James C Wade; Benedetto Bruno; Amelia Langston; Jerald Radich; Dietger Niederwieser; Karl G Blume; Rainer Storb; David G Maloney
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