Poor Mobilization of Hematopoietic Stem Cells – Definitions, Incidence, Risk Factors and Impact On Outcome of Autologous Transplantation.

Abstract

2153 Poster Board II-130 Hematopoietic progenitor and stem cells (HSC) reside in the bone marrow and have to be mobilized into the circulation prior to being collected by apheresis. The number of apheresis procedures needed and the success of transplantation are determined by the efficiency of stem cell mobilization. Between January 2004 to December 2008, 840 patients (pt) with the following diagnoses were scheduled to undergo leukapheresis for autologous transplantations: multiple myeloma (MM, n=602) and non-Hodgkin's lymphoma (NHL, n=238). Mobilization data and transplantation outcome were analyzed retrospectively. Most of the pt mobilized readily: close to 85% of the pt had a level of 20/μL to >500/μL of CD34+ cells at the peak of stimulation. Of the 840 pt, 129 (15.3%) were considered to be “Poor Mobilizers” (PM), defined as pt who had a peak concentration of <20/μL of CD34+ cells upon stimulation with G-CSF subsequent to induction chemotherapy appropriate for the respective disease. Among them, 38 (4.5%) pt had CD34+ levels of between 11-19/μL at maximum stimulation, defined as borderline PM, 49 (5.8%) pt had CD34+ levels of between 6-10/μL, defined as relative PM and 42 pt (5%) with levels of <5/μL, defined as absolute PM. We have analyzed the relationship between poor mobilizations with types of disease (MM versus NHL), sex, age, body weight, previous irradiation, number of cycles of previous combination chemotherapy, and pretreatment with melphalan. There was no difference in the incidence of PM between pt with MM versus those with NHL. Sex, age, body weight and previous irradiation therapy did not make any significant difference. Only the number of cycles of previous chemotherapy (p=0.0034), and previous treatment with melphalan (p=0.0078) had a significant impact on the ability to mobilize. Secondary strategies to mobilize HSC from the 33 who failed included: (1) Administration of another cycle of induction chemotherapy + G-CSF. The goal of harvesting 2.0 × 10exp6 CD34+ cells/kg body weight could be accomplished in 7 of 21 of these patients. (2) G-CSF alone for 4 days (up to 8 days of stimulation) after hematopoietic recovery from previous induction chemotherapy. The goal could be achieved in 2 of the 9 patients thus mobilized. (3) Plerixafor within the compassionate use program. The goal was accomplished in 7 of 8 patients within one cycle of mobilization. All 8 could be transplanted successfully. (4) Bone marrow harvest in lieu of collection of peripheral HSC in 5 patients. For the good mobilizers, the median time to recovery of the WBC to 1.0/nL or granulocyte of 0.5/nL (whichever is sooner) was 13 days with a range of 7 to 22 days, whereas for the PM group it was 14 days with a range of 8 to 37 days. This difference was statistically not significant. The median time to recovery of the platelets counts to an unmaintained level of >20/nL was 11 days with a range of 6 to 17 days for the good mobilizers, whereas for the PM it was 11 days with a range of 7 to 32 days. Again this difference was statistically not significant. The majority of the patients nowadays intended for autologous transplantations were able to mobilize readily. According to the criteria proposed in this study, 15.3% were considered to be “Poor Mobilizers”, 4.5% borderline PM, 5.8% relative PM and 5% absolute PM. No significant difference was found between patients with NHL versus MM. Sex, age, body weight and previous irradiation therapy did not make any difference. Only the number of cycles of previous chemotherapy (p=0.0034), and previous treatment with melphalan (p=0.0078) had a significant impact. Above all, as long as 2.0 × 10exp6 of CD34+ cells per kg of body weight have been collected, poor mobilization was not associated with inferior engraftment. Disclosures: No relevant conflicts of interest to declare.

Poor peripheral blood stem cell mobilization affects long‐term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation

“…Furthermore, in our program, we recommend non-lenalidomide containing induction therapy, mainly cyclophosphamide/bortezomib/dexamethasone, which may explain the lower number of patients who received lenalidomide in their first induction regimen and possibly the relatively lower frequency of poor mobilizers (10.4%), whereas many other studies reported > 15% incidence. 21,22 Another possible limitation is the relatively small number of patients treated with CXCR4 antagonist plerixafor. Due to its effectiveness in reducing the number of poor mobilizers, many institutions now routinely utilize plerixafor for PBSC mobilization.…”

“…[16][17][18][19] Most studies use different definitions for poor mobilization in MM patients, mainly due to the practice of collecting upfront adequate numbers of stem cells for two transplants. [20][21][22] Poor mobilization prior to ASCT has important prognostic implications. In lymphoma, work from our institution demonstrated poor mobilizers (defined as inability to obtain 1 3 10 6 CD341 cells/kg ideal body weight [IBW] with two large volume apheresis) had a shortened PFS and OS compared to patients who were good mobilizers.…”

Cobalt protoporphyrin IX increases endogenous G‐ CSF and mobilizes HSC and granulocytes to the blood

“…It is also applied in the treatment of various types of neutropenia (Gabrilove et al, 1988;Hoggatt & Pelus, 2014). Although G-CSF was successfully introduced to clinical practice, there are cases when G-CSF treatment remains inefficient (Wuchter et al, 2010;To et al, 2011). One of the proposed strategies to overcome these limitations would imply induction of endogenous G-CSF expression by drug administration rather than administration of recombinant G-CSF itself (Hoggatt & Pelus, 2014).…”

Successful collection of peripheral blood stem cells upon VIDE chemomobilization in sarcoma patients

“…9 The authors reported on a daily complete blood count the obtained results should be interpreted with cautiousness, as a substantial variation of mobilized stem cells can be observed and poor and mega-mobilizers can be found even in a homogeneous patient population. 26 Future studies should also analyze the role of immunocompetent cell subsets in the stem cell graft.…”