Salvage Therapy for CLL and the Role of Stem Cell Transplantation

Gribben, John G.

doi:10.1182/asheducation-2005.1.292

Cited by 20 publications

(8 citation statements)

References 44 publications

(45 reference statements)

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“…Although the efficacy of chemotherapy and antibodies as well as of autologous SCT is significantly impaired in the presence of unfavorable prognostic factors, [14][15][16] 17 In other words, current evidence indicates that allo-SCT is the only modality that is highly effective in both good-risk and poor-risk disease as defined by clinical and biological criteria.…”

Section: Cll Transplant Consensus P Dreger Et Almentioning

confidence: 99%

Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus

et al. 2006

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The aim of this project was to identify situations where allogeneic stem cell transplantation (allo-SCT) might be considered as a preferred treatment option for patients with B-cell chronic lymphocytic leukemia (CLL). Based on a MED-LINE search and additional sources, a consented proposal was drafted, refined and approved upon final discussion by an international expert panel. Key elements of the consensus are (1) allo-SCT is a procedure with evidence-based efficacy in poor-risk CLL; (2) although definition of 'poor-risk CLL' requires further investigation, allo-SCT is a reasonable treatment option for younger patients with (i) non-response or early relapse (within 12 months) after purine analogues, (ii) relapse within 24 months after having achieved a response with purineanalogue-based combination therapy or autologous transplantation, and (iii) patients with p53 abnormalities requiring treatment; and (3) optimum transplant strategies may vary according to distinct clinical situations and should be defined in prospective trials. This is the first attempt to define standard indications for allo-SCT in CLL. Nevertheless, whenever possible, allo-SCT should be performed within disease-specific prospective clinical protocols in order to continuously refine transplant indications according to new developments in risk assessment and treatment of CLL.

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Section: Cll Transplant Consensus P Dreger Et Almentioning

confidence: 99%

Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus

et al. 2006

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“…[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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“…Moreover, in III-IV Rai stage patients the percentage of ex vivo apoptotic cells after chemotherapy was lower than before therapy, whereas in I-II Rai stage patients the percentage of ex vivo apoptotic cells after chemotherapy was higher than before the treatment. It is known that the advanced stage is an unfavourable prognostic factor in B-CLL, frequently associated with resistance to chemotherapy (27,28). However, the high percentage of apoptotic cells in untreated advanced-stage patients and a positive correlation between the percentage of apoptotic cells and B-CLL stage are original and notable observations.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis in B-CLL: The relationship between higher ex vivo spontaneous apoptosis before treatment in III-IV Rai stage patients and poor outcome

Sieklucka

Pożarowski²,

Bojarska‐Junak³

et al. 2008

Oncol Rep

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B-cell chronic lymphocytic leukaemia (B-CLL) has been described as the progressive accumulation of matureappearing B cells in peripheral blood and bone marrow, resulting from failed apoptosis rather than from alterations in cell cycle regulation. Recent investigations suggest that high WBC and lymphocyte counts result not only from defects in apoptosis, but also from cell proliferation. In this study, we aimed to examine the process of apoptosis in B-CLL patients before and during anti-cancer therapy, to answer the question of whether this parameter would presage the response to treatment and the clinical course of the disease. We found that ex vivo spontaneous apoptosis was higher in advanced-stage (III-IV acc. Rai) than in early-stage (I-II acc. Rai) patients. In I-II Rai stage patients the percentage of ex vivo apoptotic cells after chemotherapy was higher than that of apoptotic cells prior to treatment, whereas in III-IV Rai stage patients the percentage of ex vivo apoptotic cells after chemotherapy was lower than that of apoptotic cells before the anti-cancer therapy. The results of our study, in the context of the cited literature, suggest a relationship between higher ex vivo spontaneous apoptosis before treatment in advanced-stage patients with a higher proliferation of leukaemic cells and poor outcome.

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Salvage Therapy for CLL and the Role of Stem Cell Transplantation

Cited by 20 publications

References 44 publications

Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus

Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus

Reduced intensity versus full myeloablative stem cell transplant for advanced CLL

Apoptosis in B-CLL: The relationship between higher ex vivo spontaneous apoptosis before treatment in III-IV Rai stage patients and poor outcome

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