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Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study.

ABSTRACT: We analysed the long-term outcomes of 60 multiple myeloma patients who underwent reduced intensity allogeneic stem cell transplantation between August 2000 and March 2008. Regimens included fludarabine and melphalan conditioning (flu-mel regimen) for allogeneic haematopoietic cell transplant (HCT) or a planned tandem regimen consisting of high-dose melphalan conditioning for autograft followed by low-dose total body irradiation conditioning for allogeneic HCT (auto-allo regimen). Donors included human-leucocyte-antigen-matched siblings (n = 55) or matched unrelated donors (n = 5). With a median follow-up of 9·8 years, 7-year overall survival (OS) and progression-free survival (PFS) were 60% and 31%, respectively. By multivariate Cox regression analysis, disease status of complete response (CR) or partial response (PR) at transplant and the presence of chronic graft-versus-host disease were significantly associated with improved OS. Only disease status was significantly associated with improved PFS. We noted a surprising number of very late relapses, with six patients (10%) relapsing between 6 and 12 years post-transplant. Among the six late relapse patients, all were transplanted within 14 months of diagnosis, five had normal karyotypes, and five were in CR/PR. Our data provide additional evidence that, while survival may be extended by reduced intensity allogeneic transplant, ultimately, it may not offer a cure.

SUBMITTER: Sahebi F

PROVIDER: S-EPMC3542410 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study.

Sahebi Firoozeh F Shen Yan Y Thomas Sandra H SH Rincon Amalia A Murata-Collins Joyce J Palmer Joycelynne J Krishnan Amrita Y AY Karanes Chatchada C Htut Myo M Somlo George G Forman Stephen J SJ

British journal of haematology 20121115 2

We analysed the long-term outcomes of 60 multiple myeloma patients who underwent reduced intensity allogeneic stem cell transplantation between August 2000 and March 2008. Regimens included fludarabine and melphalan conditioning (flu-mel regimen) for allogeneic haematopoietic cell transplant (HCT) or a planned tandem regimen consisting of high-dose melphalan conditioning for autograft followed by low-dose total body irradiation conditioning for allogeneic HCT (auto-allo regimen). Donors included ...[more]

PMID: 23151215

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Project description:We previously reported initial results in 102 multiple myeloma (MM) patients treated with sequential high-dose melphalan and autologous hematopoietic cell transplantation followed by 200 cGy total body irradiation with or without fludarabine 90 mg/m2 and allogeneic hematopoietic cell transplantation. Here we present long-term clinical outcomes among the 102 initial patients and among 142 additional patients, with a median follow up of 8.3 (range 1.0-18.1) years. Donors included human leukocyte antigen identical siblings (n=179) and HLA-matched unrelated donors (n=65). A total of 209 patients (86%) received tandem autologous-allogeneic upfront, while thirty-five patients (14%) had failed a previous autologous hematopoietic cell transplantation before the planned autologous-allogeneic transplantation. Thirty-one patients received maintenance treatment at a median of 86 days (range, 61-150) after allogeneic transplantation. Five-year rates of overall survival (OS) and progression-free survival (PFS) were 54% and 31%, respectively. Ten-year OS and PFS were 41% and 19%, respectively. Overall non-relapse mortality was 2% at 100 days and 14% at five years. Patients with induction-refractory disease and those with high-risk biological features experienced shorter OS and PFS. A total of 152 patients experienced disease relapse and 117 of those received salvage treatment. Eighty-three of the 117 patients achieved a clinical response, and for those, the median duration of survival after relapse was 7.8 years. Moreover, a subset of patients who became negative for minimal residual disease (MRD) by flow cytometry experienced a significantly lower relapse rate as compared with MRD-positive patients (P=0.03). Our study showed that the graft-versus-myeloma effect after non-myeloablative allografting allowed long-term disease control in standard and high-risk patient subsets. Ultra-high-risk patients did not appear to benefit from tandem autologous/allogeneic hematopoietic cell transplantation because of early disease relapse. Incorporation of newer anti-MM agents into the initial induction treatments before tandem hematopoietic cell transplantation and during maintenance might improve outcomes of ultra-high-risk patients. Clinical trials included in this study are registered at: clinicaltrials.gov identifiers: 00075478, 00005799, 01251575, 00078858, 00105001, 00027820, 00089011, 00003196, 00006251, 00793572, 00054353, 00014235, 00003954.

Project description:Background and objectivesIntensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT).Patients and methodsThirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617-1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk.ResultsThe mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III-IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients.ConclusionsIMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

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Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study.

Publications

Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study.

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