Unrelated stem cell transplantation for patients with multiple myeloma

Kröger, Nicolaus

doi:10.1097/moh.0b013e32833e5b01

Cited by 7 publications

(6 citation statements)

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“…All patients had failed at least 1 previous auto-HCT, and one-third had failed 2 auto-HCTs, a reflection of more advanced refractory disease. The 2-year OS of 48% in these patients compares favorably with that in allo-HCT using matched related or unrelated donors in patients with relapsed MM [20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Sahebi

Garderet

Kanate

et al. 2019

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic cell transplantation (allo-HCT) using siblings and matched donors has the potential for long-term disease control in a subset of high-risk patients with multiple myeloma (MM); however, the data on using haploidentical donors in this disease are limited. We conducted a retrospective analysis to examine the outcomes of patients with MM who underwent haploidentical allo-HCT within European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers. A total of 96 patients underwent haploidentical allo-HCT between 2008 and 2016. With a median follow-up of 24.0 months (range, 13.2 to 24.9 months), 97% (95% confidence interval [CI], 93% to 100%) of patients had neutrophil engraftment by day 28, and 75% (95% CI, 66% to 84%) achieved platelet recovery by day 60. Two-year progression-free survival (PFS) was 17% (95% CI, 8% to 26%), and overall survival (OS) was 48% (95% CI, 36% to 59%). At 2 years, the cumulative risk of relapse/progression was 56% (95% CI, 45% to 67%), and 1-year nonrelapse mortality (NRM) was 21% (95% CI, 13% to 29%). The incidences of acute graft-versus-host-disease (GVHD) grades II-IV by 100 days and chronic GVHD at 2 years were 39% (95% CI, 28% to 49%) and 46% (95% CI, 34% to 59%), respectively. On univariate analysis, use of post-transplantation cyclophosphamide (PT-Cy) (54% [95% CI, 41% to 68%] versus 25% [95% CI, 1% to 48%]; P =.009) and use of bone marrow as source of stem cells (72% [95% CI, 55% to 89%] versus 31% [95% CI, 17% to 46%]; P = .001) were associated with improved OS at 2 years. Disease status, patient sex,

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Section: Discussionmentioning

confidence: 99%

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Sahebi

Garderet

Kanate

et al. 2019

Biology of Blood and Marrow Transplantation

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“…There are only few published data of unrelated SCT in MM, these data reported a higher TRM for standard MA conditioning in comparison to RIC (5, 12, 14).…”

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confidence: 94%

“…Unlike myeloablative allo‐SCT where dose intensity intrinsically reduces tumor burden, RIC allo‐SCT depends largely on the graft‐versus‐leukemia (GVL) effect. As such, the extent of minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes (4, 5). Although this seemed to be an attractive option, it is associated with high treatment‐related mortality (TRM) mainly because of myeloablative (MA) conditioning (6).…”

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confidence: 99%

“…There is currently no generally accepted standard treatment for patients with relapsed or refractory myeloma (4, 9). Salvage allo‐SCT can be considered especially in patients at high risk of relapse occurring early after autologous stem cell transplantation (5, 10–13). The numbers of unrelated SCT for hematological diseases in Europe are higher than for human leukocyte antigen (HLA)‐identical sibling transplantations, but in multiple myeloma only 39% of the allogeneic transplantations are performed from unrelated donors and only a minority were carried out within prospective clinical trials (5).…”

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confidence: 99%

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Comparable outcomes between unrelated and related donors after reduced‐intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high‐risk multiple myeloma

El-Cheikh

Crocchiolo

Boher

et al. 2012

European J of Haematology

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The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD (P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group (P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% (P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols.

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“…The transfer of a healthy, donor-derived immune system, which is not tolerant to the malignant plasma cell clone, is currently the only potentially curative approach for MM patients [6]. The immunological graft-versus-myeloma effect (GvM) is powerful, but it comes along with a significant risk of developing a graft-versus-host reaction (GvHD), which represents a potentially deadly threat often requiring strong prophylactic (and sometimes therapeutic) immunosuppression [6, 7]. Optimized strategies are needed to determine exactly how much immunosuppression is needed to dampen harmful alloimmune reactions while still allowing for clinically required graft-versus-myeloma effects [7].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Analysis of Tetanus- and Influenza-Specific IgG Antibodies in Myeloma Patients

Kobold

Luetkens

Bartels

et al. 2012

Clinical and Developmental Immunology

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Background. Multiple myeloma (MM) and its therapies may induce a severely compromised humoral immunity. We have performed a longitudinal analysis of IgG-antibody responses against influenza virus (FLU) and tetanus toxoid (TT) as surrogate markers for the B cell-mediated immunity in MM patients.Methods. 1094 serum samples of 190 MM patients and samples from 100 healthy donors were analyzed by ELISA for FLU- and TT-specific antibodies.Results. MM patients evidenced lower levels of FLU- and TT-specific antibodies than healthy controls (P<0.001). Immunoreactivity decreased with progressing disease and worsening clinical status. Levels of FLU- and TT-specific antibodies increased shortly (0-6 months) after alloSCT (P<0.001), a time-period during which intravenous immunoglobulin (IVIG) is routinely applied. Thereafter, antibody concentrations declined and remained suppressed for 3 years in the case of FLU-specific and for more than 5 years in the case of TT-specific antibodies.Conclusions. We found that MM is associated with a profound disease- and therapy-related immunosuppression, which is compensated for a few months after alloSCT, most likely by application of IVIG. This and the differences regarding the recovery of anti-FLU and anti-TT antibody titers during the following years need to be taken into account for optimizing IVIG application and immunization after alloSCT.

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Unrelated stem cell transplantation for patients with multiple myeloma

Abstract: Unrelated SCT in multiple myeloma is feasible, but prospective clinical trials using unrelated stem cell donors are urgently needed to define the role of an unrelated SCT in multiple myeloma in the era of novel agents.

Cited by 7 publications

References 58 publications

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report

Comparable outcomes between unrelated and related donors after reduced‐intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high‐risk multiple myeloma

Longitudinal Analysis of Tetanus- and Influenza-Specific IgG Antibodies in Myeloma Patients

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