Advertisement

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre

      Abstract

      Background

      Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting.

      Methods

      We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019.

      Results

      146 patients – majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 – 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 – 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 – 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 – 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 – 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14–15 days) and 16 days (95% CI 15–16 days) respectively.

      Conclusion

      PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Transfusion and Apheresis Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dhakal B.
        • Szabo A.
        • Chhabra S.
        • et al.
        Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction: a systematic review and meta-analysis.
        JAMA Oncol. 2018; 4: 343-350https://doi.org/10.1001/jamaoncol.2017.4600
        • Philip T.
        • Guglielmi C.
        • Hagenbeek A.
        • et al.
        Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma.
        N Engl J Med. 1995; 333: 1540-1545
        • Schmitz N.
        • Pfistner B.
        • Sextro M.
        • et al.
        Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial.
        The Lancet. 2002; 359https://doi.org/10.1016/S0140-6736(02)08938-9
        • To L.B.
        • Haylock D.N.
        • Simmons P.J.
        • et al.
        The biology and clinical uses of blood stem cells.
        Blood. 1997; 89: 2233-2258
        • Bensinger W.
        • Appelbaum F.
        • Rowley S.
        • Storb R.
        • Sanders J.
        • Lilleby K.
        • et al.
        Factors that influence collection and engraftment of autologous peripheral-blood stem cells.
        J Clin Oncol. 1995; 13: 2547-2555
        • Oran B.
        • Malek K.
        • Sanchorawala V.
        • et al.
        Predictive factors for hematopoietic engraftment after autologous peripheral blood stem cell transplantation for AL amyloidosis.
        Bone Marrow Transplant. 2005; 35: 567-575https://doi.org/10.1038/sj.bmt.1704826
        • Pusic I.
        • Jiang S.Y.
        • Landua S.
        • et al.
        Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation.
        Biol Blood Marrow Transplant. 2008; 14: 1045-1056
        • To L.B.
        • Dyson P.G.
        • Juttner C.A.
        • et al.
        Cell-dose effect in circulating stem-cell autografting.
        Lancet. 1986; 2: 404-405https://doi.org/10.1016/s0140-6736(86)90096-6
        • Weaver C.H.
        • Hazelton B.
        • Birch R.
        • et al.
        An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.
        Blood. 1995; 86: 3961-3969https://doi.org/10.1182/blood.V86.10.3961.bloodjournal86103961
        • Micallef I.N.
        • Apostolidis J.
        • Rohatiner A.Z.
        • et al.
        Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-hodgkin’s lymphoma.
        Hematol J. 2000; 1: 367-373
        • Stiff P.J.
        Management strategies for the hard-to-mobilize patient.
        Bone Marrow Transplant. 1999; 23: S29-S33
        • Wuchter P.
        • Ran D.
        • Bruckner T.
        • et al.
        Poor mobilization of hematopoietic stem cells – definitions, incidence, risk factors, and impact on outcome of autologous transplantation.
        Biol Blood Marrow Transplant. 2010; 16: 490-499
        • Hosing C.
        • Saliba R.M.
        • Ahlawat S.
        • et al.
        Poor hematopoietic stem cell mobilizers: a single-institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma.
        Am J Hematol. 2009; 84: 335-337
        • Ferraro F.
        • Lymperi S.
        • Méndez-Ferrer S.
        • et al.
        Diabetes impairs hematopoietic stem cell mobilization by altering niche function.
        Sci Trans Med. 2011; 3104ra101
        • Ameen R.M.
        • Alshemmari S.H.
        • Alqallaf D.
        Factors associated with successful mobilization of progenitor hematopoietic stem cells among patients with lymphoid malignancies.
        Clin Lymphoma Myeloma. 2008; 8: 106-110
        • Kuittinen T.
        • Nousiainen T.
        • Halonen P.
        • et al.
        Prediction of mobilisation failure in patients with non- Hodgkin’s lymphoma.
        Bone Marrow Transplant. 2004; 33: 907-912
        • Akhtar S.
        • Weshi A.E.
        • Rahal M.
        • et al.
        Factors affecting autologous peripheral blood stem cell collection in patients with relapsed or refractory diffuse large cell lymphoma and Hodgkin lymphoma: a single institution result of 168 patients.
        Leuk Lymphoma. 2008; 49: 769-778
        • Mohty M.
        • Duarte R.
        • Croockewit S.
        • et al.
        The role of plerixafor in optimizing peripheral blood stem cell mobilization for autologous stem cell transplantation.
        Leukemia. 2011; 25: 1-6https://doi.org/10.1038/leu.2010.224
        • Giralt S.
        • Costa L.
        • et al.
        Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations.
        Biol Blood Marrow Transplant. 2014; 20: 295-308
        • Bolwell B.J.
        • Pohlman B.
        • Rybicki L.
        • et al.
        Patients mobilizing large numbers of CD34+ cells (‘super mobilizers’) have improved survival in autologous stem cell transplantation for lymphoid malignancies.
        Bone Marrow Transplant. 2007; 40: 437-441
        • Hübel K.
        Mobilization and collection of HSC.
        in: Carreras E. Durfour C. Mohty M. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. seventh ed. Springer Nature, Switzerland2019: 117-122
        • Döhner H.
        • Estey E.
        • Grimwalde D.
        • et al.
        Diagnosis and management of AML in adults: 2017 ELNrecommendations from an international expert panel.
        Blood. 2017; 129: 424-447
        • Song G.Y.
        • Jung S.H.
        • Ahn S.Y.
        • et al.
        Optimal chemo-mobilization for the collection of peripheral blood stem cells in patients with multiple myeloma.
        BMC Cancer. 2019; 19: 59
        • Novitzky N.
        • Thomas V.
        • du Toit C.
        • et al.
        Is there a role for autologous stem cell transplantation for patients with acute myelogenous leukemia? A retrospective analysis.
        Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2010; 17: 875-884
        • Shin H.J.
        • Chung J.S.
        • Choi Y.J.
        • et al.
        Comparison of the peripheral blood stem cell mobilization and harvest after each consolidation chemotherapy in patients with acute myeloid leukemia in first complete remission who underwent autologous stem cell transplantation.
        Blood. 2005; 106: 5495
        • Yu J.
        • Leisenring W.
        • Bensinger W.I.
        • et al.
        The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield.
        Transfusion. 1999; 39: 442-450https://doi.org/10.1046/j.1537-2995.1999.39050442.x
        • Fontao-Wendel R.
        • Lazar A.
        • Melges S.
        • et al.
        The absolute number of circulating CD34+ cells as the best predictor of peripheral hematopoietic stem cell yield.
        J Hematother. 2004; 8https://doi.org/10.1089/106161299320271
        • Gibbs G.
        • Bolam S.
        Peripheral blood CD34+ cell counts allow improved management of peripheral blood stem cell collec- tions.
        Br J Biomed Sci. 2004; 61: 35-37
        • Moncada V.
        • Bolan C.
        • Ying Yau Y.
        • Leitman S.F.
        • et al.
        Analysis of PBPC cell yields during large volume leukapheresis of subjects with a poor mobilization response to filgrastim.
        Transfusion. 2003; 43: 495-501
        • Gorin N.
        • Giebel S.
        • Labopin M.
        • et al.
        Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects.
        Bone Marrow Transplant. 2015; 50: 1495-1502https://doi.org/10.1038/bmt.2015.179
        • Bolwell B.
        • Pohlman B.
        • Rybicki L.
        • Sobecks R.
        • et al.
        Patients mobilizing large numbers of CD34 cells (‘super mobilizers’) have improved survival in autologous stem cell transplantation for lymphoid malignancies.
        Bone Marrow Transplant. 2007; 40: 437-441