High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors

Majolino, Ignazio; Corradini, Paolo; Scimè, Rosanna; Falda, Michele; Bosi, Alberto; Tarella, Corrado; Musso, Maurizio; Olivieri, Attilio; Boccadoro, Mario; Marcenò, R; Santoro, Alessandra; Pileri, Alessandro

doi:10.1038/sj.bmt.1703924

Cited by 17 publications

(12 citation statements)

References 38 publications

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“…Moreover, a more recent report from the same group (likely representing an update) included 45 patients, with 17 patients reported to have died from transplant-related complications giving an overall incidence of TRM of 38%, 49 in line with other results from Majolino et al 50 showing a 30% rate of TRM. In contrast to Majolino et al, 50 who used a full dose of busulfan and melphalan regimen, the RIC regimen used by Badros et al (melphalan 100 mg/m 2 ) is clearly of low intensity decreasing the risk of early TRM. Such a high long-term incidence of TRM might be explained by the systematic use of early preemptive DLI and a very short duration of immunosuppressive therapy.…”

Section: Discussionsupporting

confidence: 72%

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Mohty

Boiron

Damaj

et al. 2004

Bone Marrow Transplant

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Summary:In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfanbased reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P ¼ 0.006 for PFS and P ¼ 0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versusmyeloma effect with an acceptable incidence of toxicity and TRM.

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Section: Discussionsupporting

confidence: 72%

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Mohty

Boiron

Damaj

et al. 2004

Bone Marrow Transplant

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Section: Clinical Experience With Donor Lymphocyte Infusions (Dli) Inmentioning

confidence: 99%

“…[1][2][3][4][5] Although high-dose chemotherapy and total body irradiation prior transplantation effectively reduce the plasma-cell burden, donorderived immunocompetent cells have been shown to play an important role in the curative effects of allogeneic HSCT. [4][5][6][7][8] DLI alone have been demonstrated to induce response rates in 40-67% of patients with MM. [9][10][11][12][13][14][15][16][17][18][19][20] Experience was collected with DLI as prophylaxis [9][10][11][12] for myeloma relapse or as relapse treatment [13][14][15][16][17][18][19][20] after allo-HSCT.…”

Section: Clinical Experience With Donor Lymphocyte Infusions (Dli) Inmentioning

confidence: 99%

Donor lymphocyte infusions for multiple myeloma: clinical results and novel perspectives

Zeiser

Bertz

Spyridonidis

et al. 2004

Bone Marrow Transplant

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Summary:Donor lymphocyte infusions (DLIs) provide effective therapy for patients with various hematological malignancies who have relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). In patients with multiple myeloma (MM), DLIs can induce response rates of 40-52%. DLIs were employed as treatment for MM relapse or as prophylaxis for relapse in MM patients undergoing allo-HSCT. The clinically most relevant treatment-related morbidity with DLIs is the occurrence of graft-versus-host disease (GVHD). Secondly, graft failure and the immune escape of extramedullary plasmocytoma have been reported. The fact that previous clinical reports have documented graft-versus-myeloma (GVM) activity without GVHD suggests that at least two distinct immunocompetent cell populations mediating GVHD and/or GVM may exist. Further characterization of the effector cells such as T cells and/or NK cells and their targets may help to clarify the immune response that mediates the GVM effect. This review considers the results of clinical approaches with DLI for MM, with emphasis on strategies to prevent GVHD while preserving the GVM effect. Furthermore, currently investigated molecular antigenic targets for the GVM effect such as MM-specific idiotypic determinant of immunglobulin variable regions, several PRAME epitopes and antigenic structures encoded by cancer germline-specific genes as candidates for immunotherapy trials are discussed. Several studies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) can provide effective therapy for patients with MM, improve long-term survival and even cure the patient. 1-5 Although high-dose chemotherapy and total body irradiation prior transplantation effectively reduce the plasma-cell burden, donorderived immunocompetent cells have been shown to play an important role in the curative effects of allogeneic HSCT. 4-8 DLI alone have been demonstrated to induce response rates in 40-67% of patients with MM. [9][10][11][12][13][14][15][16][17][18][19][20] Experience was collected with DLI as prophylaxis 9-12 for myeloma relapse or as relapse treatment 13-20 after allo-HSCT.Although a graft-versus-myeloma (GVM) effect has been documented in several case reports and small populations, 13-18 the results must be interpreted with respect to additional chemotherapy preceding DLI administration 19 or interferon (IFN)-a 15,19 for immunological modulation. IFN-a might enhance the GVM effect by increasing the expression of cell-surface molecules necessary for the interaction of effector cells with the neoplastic plama cell 21,22 or by a direct antimyeloma effect. Although some patients seem to respond only to DLI when IFN-a is added, no randomized trial has been performed to evaluate the benefit from the cytokine in addition to DLIs. 23 Furthermore, corticosteroids, the most common employed treatment for graft-versus-host disease (GVHD) occurring after DLI, have antimyeloma activity and thus may contribute to a response.The response rates in the two larger studies (25...

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“…33 More recent studies using related donors and an ablative conditioning regimen have reported 100-day TRM rates of 16%. 18,34 A total of 47% of patients in this study developed acute Grades II-IV GVHD, although 39% of patients received a T-cell-depleted graft. The risk of GVHD reported after sibling transplants for multiple myeloma has ranged from 19 to 63%.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 Long-term, disease-free survival rates of 20-55% have been observed. 19,20 A graft-versusmyeloma effect has been demonstrated; patients with graftversus-host disease (GVHD) have a lower risk of relapse.…”

mentioning

confidence: 97%

Outcome of unrelated transplants in patients with multiple myeloma

Ballen

King

Carston

et al. 2005

Bone Marrow Transplant

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High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors

Cited by 17 publications

References 38 publications

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Donor lymphocyte infusions for multiple myeloma: clinical results and novel perspectives

Outcome of unrelated transplants in patients with multiple myeloma

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