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

Abstract

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.

Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

“…The incidence of both grade II-IV and grade III-IV acute GVHD was comparable with other studies on HCT in CLL [13,15,30] and slightly lower than with UBCT in CLL [16]. The incidence of severe acute GVHD after PTCY was slightly higher than described in other publications on haploidentical HCT with use of PTCY [18,19], but this could be just a coincidence due to the small amount of patients in this group.…”

The addition of ofatumumab to the conditioning regimen does not improve the outcome of patients with high-risk CLL undergoing reduced intensity allogeneic haematopoietic cell transplantation: a pilot trial from the GETH and GELLC (CLL4 trial)

“…All these factors led to an excessively high NRM (48% at 12 months). This NRM doubles what has been recently reported in similar studies of high-risk patients undergoing alloHCT, 5,[10][11][12] approaching what is usually accomplished with myeloablative regimens. 10,11,13 Indeed, both the PFS and the OS curves resemble those obtained with myeloablative regimens, with a very significant early attrition rate followed by a plateau.…”

Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation

“…The percentage of patients who will proceed to alloHCT among those who are originally scheduled for alloHCT might be higher with the use of pathway inhibitors than with conventional chemotherapy as bridging prior to alloHCT. 31 Yet, information on the use of pathway inhibitors for remission induction prior to alloHCT is still very preliminary and optimally 'intention-to-transplant' trials with these new drugs are warranted.…”