Feasibility of Hematopoietic Stem Cell Collection and Cryopreservation in Waldenstrom's Macroglobulinemia

Although autologous stem-cell transplantation (auto-HCT) is sporadically used in patients with Waldenström macroglobulinemia (WM), hematopoietic stem cells (HSC) are routinely collected and cryopreserved at many transplant centers after initial cytoreduction, prior to the use of myelotoxic agents like cladribine. The aim of this study is to evaluate the number of patients who underwent HSC collection, the adequacy of collection and the number of patients who eventually received auto-HCT.

We performed a retrospective chart review for 431 adult patients with WM who were seen at the University Of Texas-MD Anderson Cancer Center (MDACC). Fifty-five patients (12.8%) underwent HSC collection. Our analyses were focused on these 55 patients.

A total of 431 patients with WM were seen at our institution between 1978 and 2010. One-hundred and seven (24.8%) of these patients were referred to the Department of Stem cell Transplantation (SCT). Fifty-two patients either continued conventional therapy (31) or received plasmapheresis for hyperviscosity (21). Fifty-five (12.8%) patients underwent HSC collection either through peripheral blood (PB) HSC mobilization or bone marrow (BM) harvest. Characteristics of the 55 patients undergoing HSC collection are summarized Table 1. In 2 patients, HSC were collected by BM harvest only. Fifty-three patients underwent PB HSC mobilization with either growth factors only (34) that included filgrastim, pegfilgrastim or plerixafor; or with growth factors plus chemotherapy (19) that included cyclophosphamide alone or in combination with vincristine, doxorubicin and dexamethasone (CVAD). Out of 53 patients undergoing PBHSC mobilization, 2 patients failed to mobilize any HSC despite growth factors and chemotherapy, while 2 additional patients had inadequate HSC collection (< 2 × 10e6 CD34+ cells/kg). Forty-nine of the 53 patients undergoing PBHSC mobilization had adequate HSC collection (> 2 × 10e6 CD34 cells/kg). Overall, 51 patients (PBHSC: 49, BM harvest: 2, 93%) had an adequate (> 2 × 10e 6 CD34/kg) HSC collection. The median HSC dose collected from these patients was 6.9 × 10e6/kg ((0.5–24.1) after a median of 3 collections (1 to 7). Fifteen patients had received cladribine prior to HSC collection, and 14 (93%) of them had adequate HSC collection. However, 7/15 patients (47%) with prior cladribine required chemomobilization, in contrast to 11/39 (28%) without prior cladribine (p=0.21). In 34/51 patients with adequate collection, HSC were cryopreserved for use at the time of relapse. Thus far, 3/34 (8.8%) have gone on to receive auto-HCT after 12, 27.3 and 45.2 months, respectively. In 31/34 (91%) patients, HSC have been cryopreserved for a median duration of 24.6 months (3.1 to 187.6 months). In 17 patients, HSC were collected with the intention to immediately proceed to auto-HCT, and these patients proceeded to HDM and auto-HCT within 3 months of HSC collection (range being 0.1–2.7 months). Forty-four patients are alive after a median of 37.5 months (2.4 to 187.6) from HSC collection. Kaplan-Meier estimate of 5-year overall survival for all patients from HSC collection was 76%.

Current frontline regimens for WM are associated with high overall response rates (66–94%); however, complete remission (CR) rates (4–7%) remain low. Given the feasibility of HSC collection in patients with WM, earlier incorporation of auto-HCT for younger patients could be studied as a means of improving CR rates, and perhaps thereby improving both remission duration and overall survival.

No relevant conflicts of interest to declare.