Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status

Esteve, Jordi; Villamor, Neus; Colomer, Dolors; Cervantes, Francisco; Campo, Elı́as; Carreras, Enric; Montserrat, Emilio

doi:10.1038/sj.leu.2402036

Cited by 103 publications

(84 citation statements)

References 39 publications

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“…[1][2][3][4] Younger patients with adverse risk factors are therefore candidates for clinical trials exploring hematopoietic stem cell transplantation (HSCT). 5 Autologous HSCT is feasible and has low treatment-related mortality (TRM), but it is not curative. 6 Myeloablative allogeneic SCT (allo-HSCT) is associated with high TRM and few late relapses in CLL, 7 but is applicable to only a small number of patients.…”

Section: Introductionmentioning

confidence: 99%

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

et al. 2010

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We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P ¼ 0.82. In contrast, OS was significantly worse for MM (37% (29-48) P ¼ 0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P ¼ 0.11 and MM: 21% (18-24), P ¼ 0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.

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Section: Introductionmentioning

confidence: 99%

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

et al. 2010

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“…3,4 Autologous HCT may extend survival, but is unlikely to be curative. [4][5][6][7][8][9][10] Compelling evidence for a GVL effect in CLL rests on the observation that, even in patients with advanced diseases, long-term remissions can be achieved after allogeneic hematopoietic SCT (HCT). [11][12][13] A major drawback to these studies, which employed conventional full-intensity conditioning (FIC), was high TRM rates (up to 40%), which offset the high complete response rates.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] A major drawback to these studies, which employed conventional full-intensity conditioning (FIC), was high TRM rates (up to 40%), which offset the high complete response rates. 5,7,14,15 Recently, reduced-intensity conditioning (RIC) HCT has been used to reduce the high rates of TRM associated with FIC. [16][17][18][19] A retrospective analysis comparing RIC with FIC showed a decreased rate of upfront TRM, but an increased rate of relapse in RIC patients, resulting in equivalent 5-year overall survival (OS).…”

Section: Introductionmentioning

confidence: 99%

Reduced intensity versus full myeloablative stem cell transplant for advanced CLL

Peres

Braun

Krijanovski

et al. 2009

Bone Marrow Transplant

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CLL remains incurable with the standard therapy. Allogeneic hematopoietic stem cell transplant may be curative. We examined 50 patients with advanced CLL who underwent allogeneic HCT at the University of Michigan between 1996 and 2006. Twenty-one patients received reduced-intensity conditioning (RIC) and twentynine patients received full-intensity conditioning (FIC) consisting of CY, etoposide and BCNU (n ¼ 20) or BU and CY (n ¼ 9). RIC recipients were older than FIC recipients (median age 54 vs 51, P ¼ 0.009). There were no statistically significant differences between groups in terms of the number of earlier therapies or patients with adverse cytogenetics. There were more unrelated donors in the RIC group 62% than in the FIC group 31% (P ¼ 0.030). Despite their older age and greater use of URD, the 5-year overall survival (OS) rate was 63% in the RIC group as compared with 18% in the FIC group (P ¼ 0.006). The primary cause of inferior survival in the FIC recipients was TRM, which was twice as high at day 100 for the FIC group 27% compared with the RIC group 14% (P ¼ 0.005). The relapse rate was 15% regardless with the majority of relapses occurring after day 100. These results suggest a favorable outcome for advanced CLL who undergo a RIC regimen compared with FIC.

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“…These effective therapies and the known heterogeneity of the disease increased the importance of minimal residual disease (MRD) assessment as a surrogate marker for treatment efficiency in clinical studies. 10,12,[14][15][16][17][18] Currently, immunoglobulin heavy-chain (IgH) PCR assays with allele-specific oligonucleotide (ASO) primers are accepted as the most sensitive technique for MRD detection in CLL. 14,17,19,20 Real-time PCR using such ASO primers allows the quantitation of one CLL cell in 10 4 -10 5 cells.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation

et al. 2004

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The clinically most suitable method for minimal residual disease (MRD) detection in chronic lymphocytic leukemia is still controversial. We prospectively compared MRD assessment in 158 blood samples of 74 patients with CLL after stem cell transplantation (SCT) using four-color flow cytometry (MRD flow) in parallel with consensus IgH-PCR and ASO IgH real-time PCR (ASO IgH RQ-PCR). In 25 out of 106 samples (23.6%) with a polyclonal consensus IgH-PCR pattern, MRD flow still detected CLL cells, proving higher sensitivity of flow cytometry over PCR-genescanning with consensus IgH-primers. Of 92 samples, 14 (15.2%) analyzed in parallel by MRD flow and by ASO IgH RQ-PCR were negative by our flow cytometric assay but positive by PCR, thus demonstrating superior sensitivity of RQ-PCR with ASO primers. Quantitative MRD levels measured by both methods correlated well (r ¼ 0.93). MRD detection by flow and ASO IgH RQ-PCR were equally suitable to monitor MRD kinetics after allogeneic SCT, but the PCR method detected impending relapses after autologous SCT earlier. An analysis of factors that influence sensitivity and specificity of flow cytometry for MRD detection allowed to devise further improvements of this technique.

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Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status

Cited by 103 publications

References 39 publications

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

Reduced intensity versus full myeloablative stem cell transplant for advanced CLL

Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation

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