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. 2021 Jul 27;5(14):2879-2889.
doi: 10.1182/bloodadvances.2020003726.

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter's transformation

Oscar B Lahoud  1 , Sean M Devlin  2 , Molly A Maloy  1 , Lindsey E Roeker  3 , Parastoo B Dahi  1 , Doris M Ponce  1 , Boglarka Gyurkocza  1 , Guenther Koehne  1 , James W Young  1 , Hugo R Castro-Malaspina  1 , Juliet N Barker  1 , Esperanza B Papadopoulos  1 , Ann A Jakubowski  1 , Andrew D Zelenetz  4 , Anthony R Mato  3 , Sergio A Giralt  1 , Miguel A Perales  1 , Craig S Sauter  1
Affiliations

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter's transformation

Oscar B Lahoud et al. Blood Adv. .

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter's transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Survival outcomes of CLL patients from the time of HSCT. Data include 1. OS, 2. PFS, and 3. GRFS.
Figure 2.
Figure 2.
OS of CLL patients from the time of transplant. Patients are stratified by number of previous lines of therapy (A), remission status at the time of transplantation (B) (treatment-sensitive: CR or PR; refractory: SD or PD), use of novel agent (C), and use of TBI-containing conditioning regimen (D). Bcl-2i, Bcl-2 inhibitor; TKI, tyrosine kinase inhibitor.
Figure 3.
Figure 3.
Survival outcomes of CLL patients from the time of HSCT. Patients are stratified by manifestation of RT, including OS (A), PFS (B), and GRFS (C).
Figure 4.
Figure 4.
OS of CLL-RT patients. Patients are stratified by number of previous lines of therapy (A), age (B), and HSCT-CI score (C).
See this image and copyright information in PMC

References

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