Single versus Double Autologous Stem-Cell Transplantation for Multiple Myeloma

Attal, Michel; Harousseau, Jean‐Luc; Facon, Thierry; Guilhot, Joëlle; Doyen, Chantal; Fuzibet, J. G.; Monconduit, M.; Hulin, Cyrille; Caillot, Denis; Bouabdallah, Réda; Voillat, Laurent; Sotto, Jean‐Jacques; Grosbois, B.; Bataille, Régis

doi:10.1056/nejmoa032290

Cited by 968 publications

(741 citation statements)

References 20 publications

(14 reference statements)

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“…Further, in a Spanish randomized trial, patients responding to induction therapy failed to benefit from ASCT trial, suggesting that the greatest benefit from early ASCT may be mainly among the small proportion of patients with disease refractory to induction therapy [92]. Two randomized trials have found benefit with tandem (double) versus single ASCT, with the benefit primarily seen in patients failing to achive CR or VGPR with the first ASCT [93,94]. Two other randomized trials, however, have yet to show significant improvement in OS with double ASCT [95,96].…”

Section: Role Of Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Role Of Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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“…Most randomised trials comparing single with tandem ASCT have shown no benefit in overall survival from tandem stem cell transplantation (Attal et al, 2003;Fermand et al, 2005b;Cavo et al, 2007;Mai et al, 2016;Sonneveld et al, 2007; reviewed by Kumar et al, 2009). Many of these trials utilised non-standard conditioning regimens (e.g.…”

Section: Tandem Transplantsmentioning

confidence: 99%

“…Many of these trials utilised non-standard conditioning regimens (e.g. oral busulfan or TBI) which have since been shown to be inferior to standard mel200 (Attal et al, 2003;Fermand et al, 2005b;Cavo et al, 2007;Sonneveld et al, 2007). However the GMMG-HD2 trial, which used tandem standard mel200 ASCT, showed no difference in survival (Mai et al, 2016).…”

Section: Tandem Transplantsmentioning

confidence: 99%

“…However the GMMG-HD2 trial, which used tandem standard mel200 ASCT, showed no difference in survival (Mai et al, 2016). The only trial to show a significant benefit for both PFS and OS was the IFM-94 study, but the outcomes (in both groups) were poor compared with more recent trials using newer agents as part of the treatment protocol (Attal et al, 2003). In a nonrandomized comparison between the Dutch protocol (single transplant) and the German protocol (tandem ASCT), the latter was superior for overall survival, but regional variations in demographics and treatment could account for this difference (Sonneveld et al, 2013).…”

Section: Tandem Transplantsmentioning

confidence: 99%

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Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Maybury

Cook

Pratt

et al. 2016

Biology of Blood and Marrow Transplantation

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SummaryConsolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT) is the standard of care for transplant eligible patients with multiple myeloma, based on randomised trials showing improved progression free survival with autologous transplantation following combination chemotherapy induction. These trials were performed before novel agents were introduced, and subsequently combinations of immunomodulatory drugs (IMiDs) and proteasome inhibitors as induction therapy have significantly improved rates and depth of response. Ongoing randomised trials are testing whether conventional autologous transplantation continues to improve responses following novel agent induction. While these results are awaited, it is important to review strategies for improving outcomes following ASCT. Conditioning prior to ASCT with higher doses of melphalan, and combinations of melphalan with other agents, including radiopharmaceuticals have been explored. Tandem ASCT, consolidation and maintenance therapy following ASCT have been investigated in phase III trials. Experimental cellular therapies using ex vivo primed dendritic cells , ex vivo expanded autologous lymphocytes, KIR-mismatched allogeneic NK cells, and genetically modified T cells are also in phase I trials to augment ASCT. This review summarises these strategies and highlights the importance of exploring strategies to augment ASCT even in the era of novel agent induction.

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“…These include sequential HDCT [20,21] or more courses of HDCT [22], as reported for multiple myeloma [23]. Indeed, even in patients in complete remission after a single HDCT course, the assumption can be made that lymphoma cells are not detectable but still present, and are responsible for a subsequent relapse.…”

Section: Introductionmentioning

confidence: 99%

Tandem high‐dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: A monocenter prospective study

et al. 2006

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We designed a prospective study to evaluate the feasibility and efficacy of tandem highdose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive patients received a first HDCT course with melphalan 200 mg/m 2 (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34 + cells was 4.7 x 10 6 /kg after MEL200 and 5.8 x 10 6 /kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention-to-treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL. Am. J. Hematol. 82:122-127, 2007. V V C 2006 Wiley-Liss, Inc.

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Single versus Double Autologous Stem-Cell Transplantation for Multiple Myeloma

Abstract: As compared with a single autologous stem-cell transplantation after high-dose chemotherapy, double transplantation improves overall survival among patients with myeloma, especially those who do not have a very good partial response after undergoing one transplantation.

Cited by 968 publications

References 20 publications

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Tandem high‐dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: A monocenter prospective study

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