Molecular and Clinical Remissions in Multiple Myeloma: Role of Autologous and Allogeneic Transplantation of Hematopoietic Cells

Corradini, Paolo; Voena, Claudia; Tarella, Corrado; Astolfi, Monica; Ladetto, Marco; Palumbo, Antônio; Lint, Maria Teresa Van; Bacigalupo, Andrea; Santoro, Alessandra; Musso, Maurizio; Majolino, Ignazio; Boccadoro, Mario; Pileri, Alessandro

doi:10.1200/jco.1999.17.1.208

Cited by 224 publications

(146 citation statements)

References 28 publications

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“…The most likely explanation of the high incidence of relapse after auto-SCT1 or the use of novel agents even after the CR achieved is the persistence of residual clonal myeloma cells. 19 Auto-SCT2 has been employed in the management of recurrent MM by several groups. [9][10][11][12][13][14][15][16][17] In the era of novel agents, our study tries to define the role of an auto-SCT2 as salvage therapy in patients who have had a previous auto-SCT (auto-SCT1).…”

Section: Discussionmentioning

confidence: 99%

Second auto-SCT for treatment of relapsed multiple myeloma

Gonsalves

Gertz

Lacy

et al. 2012

Bone Marrow Transplant

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High-dose therapy and auto-SCT remain integral in the initial treatment of multiple myeloma (MM), and are increasingly being applied for management of relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto-SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1) between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74). The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130). Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was 10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2 was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher number of treatment regimens before auto-SCT2 and a higher plasma cell labeling index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an effective and feasible therapeutic option for MM patients relapsing after other treatments, especially in patients who had a TTP of at least 12 months after their auto-SCT1.

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Section: Discussionmentioning

confidence: 99%

Second auto-SCT for treatment of relapsed multiple myeloma

Gonsalves

Gertz

Lacy

et al. 2012

Bone Marrow Transplant

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“…However, the chance of definitive cure with this treatment modality is low, especially in patients with high-risk parameters (Desikan et al, 2000). Following allogeneic stem cell transplant (allo-SCT), 30-50% of patients with advanced MM who survive the first year post transplant remain disease free at 3-6 years, with well-documented cases of sustained molecular remissions (Corradini et al, 1999), probably as a result of a graftversus-myeloma effect. Unfortunately, transplant-related mortality (TRM) in the first 100 d has been observed to be 30-50% (Gahrton et al, 1991;Bensinger et al, 1996), and even higher in patients progressing after high-dose therapy and autologous stem cell transplantation (SCT; 50-80%; Kulkarni et al, 1999).…”

mentioning

confidence: 99%

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Einsele¹,

Schäfer²,

Hebart³

et al. 2003

Br J Haematol

107

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Summary. Allogeneic stem cell transplantation (allo‐SCT) after reduced‐intensity conditioning was evaluated in 22 patients (median age 53, range 36–66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)‐identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA‐mismatched unrelated donor]. Graft‐versus‐host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) (n = 12) or CSA plus mycophenolate mofetil (n = 10). Despite of heavy pretreatment, the transplant‐related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2–19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8–36 months) post allografting. Estimated 2 year overall and event‐free survival was, respectively, 25·5% and 22·0% for the whole patient group, and 62·5% and 57·1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation (P = 0·0182) and absence of cGVHD (P = 0·069) were associated with shorter event‐free survival. Thus long‐term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.

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“…In multiple myeloma cell lines, the cytotoxicity of treosulfan was equal or superior to that of melphalan. 18,19 Its organ toxicities are limited, even near the maximum tolerable dose of 47 g/ m 2 . 20,21 The substance has very recently been introduced in the allogeneic stem cell setting in combination with fludarabine or cyclophosphamide.…”

Section: Introductionmentioning

confidence: 99%

“…1 This approach leads to a complete response (CR) in a significant proportion of patients, even in those who relapsed after autologous stem cell transplantation (ASCT) or showed progressive disease (PD) before allogeneic SCT. 2,3 However, allogeneic SCT with conventional conditioning is limited to younger patients who lack major comorbidity. To make it applicable in elderly patients and minimize treatment-related mortality (TRM) in younger ones, reduced-intensity conditioning (RIC) regimens have been developed in recent years.…”

Section: Introductionmentioning

confidence: 99%

Reduced-toxicity conditioning with fludarabine and treosulfan prior to allogeneic stem cell transplantation in multiple myeloma

Schmidt‐Hieber

Blau

Trenschel

et al. 2007

Bone Marrow Transplant

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In recent years, reduced-intensity conditioning (RIC) regimens before allogeneic stem cell transplantation (SCT) are increasingly used in patients not eligible for conventional conditioning. We did a retrospective, multicenter analysis to assess the feasibility of conditioning with fludarabine and treosulfan before allogeneic SCT in multiple myeloma patients. Thirty-four patients with a median age of 51.5 years were included in the analysis. All patients underwent myeloablation after conditioning followed by stable engraftment, and 29 of 31 evaluable patients (94%) showed early complete hematopoietic chimerism. Non-hematological toxicities were limited and encompassed mainly fever in neutropenia and infections. Grade II-IV acute and chronic graft-versushost disease was observed in 33 and 39%, respectively. With a median follow-up of 708 days (range 60-1729 days), the median progression-free survival was 180 days. The treatment-related mortality was 10% on day 100 and 25% after 1 year. The median overall survival has not yet been reached. Our data indicate that conditioning with fludarabine and treosulfan before allogeneic SCT is feasible in intensively pretreated multiple myeloma patients and leads to stable engraftment and complete hematopoietic chimerism. Randomized trials are warranted to determine if this approach might be incorporated in an algorithm of multiple myeloma treatment.

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Molecular and Clinical Remissions in Multiple Myeloma: Role of Autologous and Allogeneic Transplantation of Hematopoietic Cells

Cited by 224 publications

References 28 publications

Second auto-SCT for treatment of relapsed multiple myeloma

Second auto-SCT for treatment of relapsed multiple myeloma

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Reduced-toxicity conditioning with fludarabine and treosulfan prior to allogeneic stem cell transplantation in multiple myeloma

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