Hematopoietic cell transplantation for Waldenström macroglobulinemia

Abstract

Waldenstro¨m macroglobulinemia (WM) is a distinct indolent B-cell lymphoproliferative malignancy characterized by IgM paraproteinemia. Although the disease is sensitive to chemo-immunotherapy, it remains incurable and affected patients have a median survival of 5-10 years. Risk stratification in newly diagnosed patients should start with a prognostic evaluation based on the International Prognostic Scoring System for WM (IPSSWM) to identify those patients in whom particularly poor survival with chemotherapy is expected and in whom alternative treatment strategies, such as hematopoietic cell transplantation (HCT), should be considered. High-dose chemotherapy followed by autologous HCT (auto-HCT) results in disease-free survival of 45-65% at 5 years, but is unlikely to be curative. Chemosensitive disease at the time of auto-HCT is the most important prognostic factor for response rate and overall survival. Allogeneic donor HCT may offer a unique immunemediated GVL effect with a plateau in relapse rates and potential for extended disease-free survival. The risk of allogeneic HCT complications is justified in HCT-eligible patients whose expected survival is o5 years. Here, we present the advances in non-transplant strategies and the therapeutic role of transplant, and suggest a treatment algorithm for selecting a HCT strategy while adhering to current evidence supporting autologous and allogeneic donor HCT for WM.

Waldenström macroglobulinemia: What a hematologist needs to know

“…Only a modest, 10% reduction in 3-year TRM was observed with the reduced-intensity compared to myeloablative conditioning in a large EBMTR series, with 3-year relapse rates of 25% and 11%, respectively [116]. As such, it should ideally be avoided outside of controlled clinical trials [115]. However, given the paucity of data from clinical trials, one could arguably justify performing a nonmyeloablative allogeneic hematopoietic stem cell transplantation in a rare fit patient with multi-resistant disease and limited alternatives [117].…”

“…Owing to a lack of evidence for survival benefit, ASCT is not recommended as a primary consolidative approach outside of a controlled clinical trial [115]. The cryopreserved cells could be used at first progression [20].…”

Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management

“…Among 158 patients, the median reported survival was 9.2 years. The response rate reported is 90%; the relapse‐free survival rate is 65% at 3 years …”

Genetic Factors and Pathogenesis of Waldenström’s Macroglobulinemia

“…[15, 24] In certain high-risk patients, high-dose chemotherapy followed by autologous or allogeneic hematopoietic cell transplantation may increase progression-free survival. [25]…”