Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989

Blood - Tập 111 - Trang 94-100 - 2008
Bart Barlogie1, Guido Tricot1, Jeff Haessler2, Frits van Rhee1, Michele Cottler-Fox1,3, Elias Anaissie1, James Waldron3, Mauricio Pineda-Roman1, Raymond Thertulien1, Maurizio Zangari1, Klaus Hollmig1, Abid Mohiuddin1, Yazan Alsayed1, Antje Hoering2, John Crowley2, Jeffrey Sawyer1,3
1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Seattle, WA
2Cancer Research and Biostatistics, Seattle, WA; and
3Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Seattle, WA

Tóm tắt

Myelodysplastic syndrome (MDS) is a well-recognized complication of chemotherapy for multiple myeloma (MM). Serial bone marrow metaphase examinations were performed for MM restaging in 3077 patients undergoing high-dose therapy (HDT). MDS-associated cytogenetic abnormalities (MDS-CAs) were observed in 105 of 2418 patients in whom cytogenetic data were available after HDT. MDS-CAs occurred transiently in 72 patients and on 3 successive occasions (persistent MDS-CAs) in 33 patients, for 10-year estimates of 4% and 2%, respectively; only 21 patients developed overt clinical MDS and 5, acute myeloblastic leukemia (AML). MDS-CA development was linked to lower CD34 yield at collection, longer time interval from MM diagnosis to HDT, older age, and lower platelet recovery after HDT; persistent MDS-CAs were predicted by CD34 yield of less than 3 × 106/kg and need for more than 2 apheresis procedures. Applying a tertile frequency distribution over time to all 105 patients with MDS-CAs, its detection early after HDT was associated with longer time interval from diagnosis and low pre-HDT platelet count (likely resulting from pre-HDT damage), whereas late-onset MDS-CAs were noted among patients treated with Total Therapy 2 and Total Therapy 3 that applied post-HDT consolidation chemotherapy (suggesting possible post-HDT damage). While the risk of MDS-CAs was low and clinical MDS occurred infrequently, monitoring after post-HDT consolidation chemotherapy appears warranted.

Tài liệu tham khảo

Attal, 1996, A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: Intergroupe Francais du Myelome., N Engl J Med, 335, 91, 10.1056/NEJM199607113350204 Child, 2003, High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma., N Engl J Med, 348, 1857, 10.1056/NEJMoa022340 Attal, 2003, Single versus double autologous stem-cell transplantation for multiple myeloma., N Engl J Med, 349, 2495, 10.1056/NEJMoa032290 Barlogie, 1997, Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma., Blood, 89, 789, 10.1182/blood.V89.3.789 Barlogie, 2006, Long-term outcome results of the first tandem autotransplant trial for multiple myeloma., Br J Haematol, 135, 1365, 10.1111/j.1365-2141.2006.06271.x Desikan, 2000, Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities., Blood, 95, 4008, 10.1182/blood.V95.12.4008 Singhal, 1996, Feasibility and efficacy of third transplant procedures in myeloma [abstract]., Blood, 88, 611a Lee, 2002, Transplantation as salvage therapy for high-risk patients with myeloma in relapse., Bone Marrow Transplantation, 30, 873, 10.1038/sj.bmt.1703715 Shulman, 1993, Therapy related second malignanies., Hematol Oncol Clin North Am, 7, 325, 10.1016/S0889-8588(18)30243-0 Kaldor, 1990, Leukemia following Hodgkin's disease., N Engl J Med, 322, 7, 10.1056/NEJM199001043220102 Levine, 1992, Is aplastic anaemia a preleukaemic disorder?, Brit J Haem, 19, 47 Le Beau, 1986, Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes No. 5 and 7., J Clin Oncol, 4, 325, 10.1200/JCO.1986.4.3.325 Kantarjian, 1986, therapy-related leukemia and myelodysplastic syndrome: clinical, cytogenetic, and prognostic features., J Clin Oncol, 4, 1748, 10.1200/JCO.1986.4.12.1748 Whitlock, 1991, Epipodophyllotoxin-related leukemia. Identificaton of a new subset of secondary leukemia., Cancer, 3, 600, 10.1002/1097-0142(19910801)68:3<600::AID-CNCR2820680326>3.0.CO;2-F Smith, 1999, Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins., J Clin Oncol, 17, 569, 10.1200/JCO.1999.17.2.569 Kushner, 1998, High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors., J Clin Oncol, 16, 3016, 10.1200/JCO.1998.16.9.3016 van Leeuwen, 1994, Leukemia risk following Hodgkin's disease: relation to cumulative dose of alkylating agents, treatment with teniposide combinations, number of episodes of chemothrapy and bone marrow damage., J Clin Oncol, 12, 1063, 10.1200/JCO.1994.12.5.1063 Armitage, 2003, Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients., J Clin Oncol, 21, 897, 10.1200/JCO.2003.07.113 Krishnan, 2000, Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors., Blood, 95, 1588, 10.1182/blood.V95.5.1588.005k38_1588_1593 Govindarajan, 1996, Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma., Br J Haematol, 95, 349, 10.1046/j.1365-2141.1996.d01-1891.x Tricot, 2002, Treatment-related myelodysplastic syndromes (t-MDS) after autotransplants for multiple myeloma [abstract]., Blood, 100, 97a Tricot, 2005, Low frequency of treatment-related myelodysplastic syndromes (t-MDS) after autotransplants (AT) for multiple myeloma (MM), especially if AT is applied early during treatment., Blood, 106, 706, 10.1182/blood.V106.11.706.706 Abruzzese, 1999, Detection of abnormal pretransplant clones in progenitor cells of patients who developed myelodysplasia after autologous transplantation., Blood, 94, 1814 Lillington, 2001, Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma., J Clin Oncol, 19, 2472, 10.1200/JCO.2001.19.9.2472 Tricot, 1995, Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities., Blood, 86, 4250, 10.1182/blood.V86.11.4250.bloodjournal86114250 Jacobson, 2003, MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants., Brit J Haematol, 133, 430, 10.1046/j.1365-2141.2003.04455.x Sawyer, 1995, Cytogenetic findings in 200 patients with multiple myeloma., Cancer Genet Cytogenet, 82, 41, 10.1016/0165-4608(94)00284-I Barlogie, 1999, Total therapy with tandem transplants for newly diagnosed multiple myeloma., Blood, 93, 55, 10.1182/blood.V93.1.55 Barlogie, 2006, Effect of adding thalidomide to the treatment of multiple myeloma with tandem autotransplants., New Engl J Med, 10, 1021, 10.1056/NEJMoa053583 Shaughnessy, 2007, A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1., Blood, 109, 2276, 10.1182/blood-2006-07-038430 van Rhee, 2007, High serum free-light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis., Blood, 110, 827, 10.1182/blood-2007-01-067728 Barlogie, 2007, Incorporating bortezomib into upfront treatment for multiple myeloma: early results of Total Therapy 3., Br J Haematol, 138, 176, 10.1111/j.1365-2141.2007.06639.x Mills, 1995, BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma., J Clin Oncol, 13, 588, 10.1200/JCO.1995.13.3.588 Kaplan, 1958, Nonparametric estimation from incomplete observations., J Am Stat Assoc, 53, 457, 10.1080/01621459.1958.10501452 Mantel, 1966, Evaluation of survival data and two new rank order statistics arising in its consideration., Cancer Chemother Rep, 50, 163 Gooley, 1999, Estimation of failure probabilities in the presence of competing risks: new representations of old estimators., Stat Med, 18, 695, 10.1002/(SICI)1097-0258(19990330)18:6<695::AID-SIM60>3.0.CO;2-O Kruskal, 1952, Use of ranks in the one-criterion variance analysis., J Am Stat Assoc, 47, 583, 10.1080/01621459.1952.10483441 Armitage, 1955, Test for linear trends in proportions and frequencies., Biometrics, 11, 375, 10.2307/3001775 Cox, 1972, Regression models and life-tables., J R Stat Soc (B), 34, 187 Bathia, 2005, Longitudinal assessment of hematopoietic abnormalities alter autologous hematopoietic cell transplantation for lymphoma., J Clin Oncol, 23, 6699, 10.1200/JCO.2005.10.330
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Blood

Tập 111

94-100

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