The impact of allogeneic stem cell transplantation on the natural course of poor-risk chronic lymphocytic leukemia as defined by the EBMT consensus criteria: a retrospective donor versus no donor comparison

Herth, Isabelle; Dietrich, Sascha; Benner, Axel; Hegenbart, Ute; Rieger, Michael A.; Stadtherr, Peter; Bondong, Andrea; Tran, Thuong Hien; Weide, Rudolf; Hensel, Manfred; Knauf, Wolfgang; Franz-Werner, Judith; Welslau, Manfred; Procaccianti, Maria; Görner, Martin; Meißner, Julia; Luft, Thomas; Schönland, Stefan; Witzens-Harig, Mathias; Zenz, Thorsten; Ho, A. D.; Dreger, Peter

doi:10.1093/annonc/mdt511

Cited by 35 publications

(22 citation statements)

References 26 publications

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“…This indicates that patients fitting the entry criteria of this study may fare better when treated with alloSCT than with non-alloSCT (immune-)chemotherapy based treatments, which is in line with a recent retrospective donor vs no donor comparison. 38 The 58% ORR to R-DHAP compares favorably with recent publications on the use of platinum and cytarabine in high-risk CLL, 20,36,37 and we confirmed that the response rate is independent of the presence of del(17p). Infections were common during R-DHAP remission induction, but it must be emphasized that strict adherence to the use of bacterial prophylaxis as was mandated from the 16th patient prevented the occurrence of severe sepsis.…”

Section: Discussionsupporting

confidence: 87%

“…The use of BCRi for the purpose of bridging high-risk patients to alloSCT may seem obvious because of their high efficacy including reduction of lymph node size and their low toxicity profile 43,45 which may lead to a higher transplant rate than observed in this prospective (67%) and another, retrospective, study (60%), 38 but it is up to now unknown what percentage of transplanted patients after BCRi induction develop rapidly progressive disease shortly after alloSCT as anecdotally communicated. The pros and cons of continuing BCRi post alloSCT are also unknown as there are concerns for a possible higher incidence of GvHD under either idelalisib or ibrutinib because of inhibition of regulatory T-cell function 48 and increased Th1 T-cell activity, 49 respectively.…”

Section: Discussionmentioning

confidence: 88%

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Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

Gelder

Oers

Alemayehu³

et al. 2016

Bone Marrow Transplant

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Allogeneic stem cell transplantation (alloSCT) remains the only curative option for CLL patients. Whereas active disease at the time of alloSCT predicts poor outcome, no standard remission-induction regimen exists. We prospectively assessed outcome after cisplatin-containing immune-chemotherapy (R-DHAP) followed by alloSCT in 46 patients (median age 58 years) fulfilling modified European Society for Blood and Marrow Transplantation (EBMT) CLL Transplant Consensus criteria being refractory to or relapsed (R/R) o1 year after fludarabine or o 2 years after fludarabine-based immunochemotherapy or R/R with del(17p). Twenty-nine patients received ⩾ 3 cycles of R-DHAP and sixteen o 3 cycles (4 because of disease progression, 8 for toxicity and 4 toxic deaths). Overall rate of response to R-DHAP was 58%, 31 (67%) proceeded to alloSCT after conditioning with fludarabine and 2 Gy TBI. Twenty (65%) remained free from progression at 2 years after alloSCT, including 17 without minimal residual disease. Intention-totreat 2-year PFS and overall survival of the 46 patients were 42 and 51% (35.5 months median follow-up); del(17p) or fludarabine refractoriness had no impact. R-DHAP followed by alloSCT is a reasonable treatment to be considered for high-risk CLL patients without access or resistance to targeted therapies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 88%

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

Gelder

Oers

Alemayehu³

et al. 2016

Bone Marrow Transplant

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“…For assigning individual patients to an EBMT risk category, a hierarchical procedure was followed by giving TP53 abnormalities priority over fludarabine refractoriness, and fludarabine refractoriness priority over early relapse after intensive therapy. 18 Primary end point was to determine the proportion of patients who achieved MRD negativity in the absence of clinical events (relapse, graft failure, NRM) at the 12-month landmark.…”

Section: Study Design and Patient Eligibilitymentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse

Hahn

Böttcher

Dietrich

et al. 2015

Bone Marrow Transplant

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To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.

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“…However, a recent retrospective study that compared patients with HR-CLL with transplant indication (according to the European Society for Blood and Marrow Transplantation criteria) in a donor-versus-no-donor analysis suggested a survival advantage for patients with an available donor. 50 Likewise, a survival advantage for HSCT was also found in a systematic meta-analysis using a Markov decision model. 51 Is HSCT effective in patients with a history of Richter's transformation?…”

Section: 25mentioning

confidence: 80%

Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?

Dreger

Schetelig

Andersen

et al. 2014

Blood

182

107

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Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (HR-CLL; ie, refractory to purine analogs, short response [<24 months] to chemoimmunotherapy, and/or presence of del[17p]/TP53 mutations). Currently, treatment algorithms for HR-CLL are being challenged by the introduction of novel classes of drugs. Among them, BCR signal inhibitors (BCRi) and B-cell lymphoma 2 antagonists (BCL2a) appear particularly promising. As a result of the growing body of favorable outcome data reported for BCRi/BCL2a, uncertainty is emerging on how to advise patients with HR-CLL about indication for and timing of HSCT. This article provides an overview of currently available evidence and theoretical considerations to guide this difficult decision process. Until the risks and benefits of different treatment strategies are settled, all patients with HR-CLL should be considered for treatment with BCRi/BCL2a. For patients who respond to these agents, there are 2 treatment possibilities: (1) performing an HSCT or (2) continuing treatment with the novel drug. Individual disease-specific and transplant-related risk factors, along with patient’s preferences, should be taken into account when recommending one of these treatments over the other.

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The impact of allogeneic stem cell transplantation on the natural course of poor-risk chronic lymphocytic leukemia as defined by the EBMT consensus criteria: a retrospective donor versus no donor comparison

Cited by 35 publications

References 26 publications

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study

Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse

Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?

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