Comparative Efficacy of Tandem Autologous Versus Autologous Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4519-4519
Author(s):  
Mohamed A. Kharfan-Dabaja ◽  
Mehdi Hamadani ◽  
Tea Reljic ◽  
William I. Bensinger ◽  
Benjamin Djulbegovic ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Group Versus ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Newly Diagnosed ◽  
Sibling Donor

Abstract Abstract 4519 Background: Despite advances in our understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM) coupled with availability of more effective therapies, it remains an incurable disease. Combining cytoreduction from high-dose (chemo- or chemoradio-) therapy with adoptive immunotherapy forms the basis of an autologous-allogeneic (auto-allo) hematopoietic cell transplantation (HCT) strategy. However, when an auto-allo HCT approach is compared to tandem autologous (auto-auto) HCT, conflicting results have been reported. Accordingly, we performed a systematic review of published studies comparing auto-auto HCT with auto-allo HCT in patients with newly diagnosed MM. Methods: A systematic search of MEDLINE thru Nov 5, 2011, and pertinent conference proceedings, was conducted. Included studies allocated newly diagnosed MM patients to auto-allo HCT if an HLA-matched sibling donor was available versus auto-auto if sibling donor was not available (biologic randomization). Independent, dual data extraction was performed. Pooling of data from similar outcomes was done using the random-effects model. Results: Our search identified 152 publications, of which five (manuscript=four, abstract=one) met inclusion criteria. The five included trials enrolled 1538 patients (auto-allo=565, auto-auto=973). At least a very good partial response was assessed in one study (522 patients) and did not differ among the treatment arms [risk ratio (RR) (95% CI) = 0.97 (0.87–1.09), p=0.66]; but complete remission, assessed in five studies (1130 patients), was higher in the auto-allo HCT arm [RR(95% CI) =1.65 (1.25–2.19), p=0.0005]. Event-free survival did not differ among auto-allo HCT group versus auto-auto HCT group on per-protocol analysis [hazard ratio (HR) (95% CI) = 0.78 (0.58–1.05)), p=0.11] of three trials (409 patients), or ITT analysis [HR(95% CI) = 0.83 (0.60–1.15), p=0.26] in three trials (1229 patients). Overall survival (OS) did not differ among these treatment arms whether analyzed on per-protocol [HR(95% CI) = 0.88 (0.33–2.35), p=0.79] in two trials (214 patients), or by ITT [HR(95% CI) = 0.80 (0.48–1.32), p=0.39] analysis in three trials (1229 patients). Non-relapse mortality (NRM) was worse with auto-allo HCT [RR(95%CI) = 3.55 (2.17–5.80), p<0.00001] in four trials (1047 patients). Conclusion: Despite higher CR rates, there is no apparent improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

Treatment of Recurrent or Persistent AML/MDS After Allogeneic Hematopoietic Cell Transplantation with Azacitidine.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1288-1288
Author(s):  
Jennifer Vaughn ◽  
Barry Storer ◽  
Marco Mielcarek ◽  
Edus H. Warren ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Case Series ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Persistent Disease ◽  
Relapsed Disease

Abstract Abstract 1288 Recurrence or persistence of disease after hematopoietic cell transplantation (HCT) remains a significant obstacle in the treatment of patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndromes (MDS). Standard therapies for relapsed disease include withdrawal of immunosuppression (WIS), donor lymphocyte infusion, induction chemotherapy, and in selected patients, a second HCT. Regardless of the intervention chosen, survival for post-transplant relapse has been dismal. Effective therapies without significant toxicity are needed. Azacitidine, a DNA demethylating agent, is the only non-HCT therapy shown to prolong survival in patients with MDS. It has also shown efficacy in patients with AML when used alone as induction or consolidation therapy or in combination with the anti CD-33 antibody gemtuzumab. Its use following HCT was inspired by the discovery of the drug's potential to enhance the graft-versus-leukemia effect through demethylation of the KIR regions on donor NK cells and by enhancing HLA-DR2 expression on leukemic blasts. It has also been shown to modulate T-cells post-engraftment and may result in lower rates of GVHD without impairing the GVL effect. Several small case series have been published evaluating azacitidine as therapy for treatment of relapse following HCT and have demonstrated improvement in disease status. None of these studies have examined azacitidine in the setting of persistent disease, which has become more relevant with the use of lower intensity conditioning regimens and the use of new methods to detect the presence of disease at extremely low levels. In this retrospective study, we determined the outcomes of patients treated with azacitidine (75 mg/m2/day for 7 days +/− gemtuzumab (3mg/m2) on day 9, every 4 weeks) for post-HCT recurrence or persistence of AML/MDS. Azacitidine treatment was initiated following HCT if there was evidence of recurrent or persistent disease (defined as any recurrent abnormal blasts detected by flow on peripheral blood or marrow or recurrent cytogenetic abnormalities). Seventeen (74%) of the patients had AML while 6 (26%) had MDS. FAB subtypes of the latter included RAEB (3), RA (1), CMML (1) and unclassified (1). Eighteen (78%) patients underwent conventional high dose conditioning, and 5 (22%) patients underwent nonmyeloablative conditioning prior to HCT. Eleven (48%) of patients had low risk cytogenetics, 3 (13%) had intermediate risk, and 9 (39%) had high risk cytogenetics. Seventeen (74%), 0 (0%) and 6 (26%) of patients were diagnosed with persistent or relapsed disease within 100, 100–200 and > 200 days following HCT. Patients began azacitidine 0–242 (median: 17) days from time of relapse and completed a median of 2 azacitidine cycles (range 1–8). Overall 6-month survival from the day of relapse was 57% and from start of azacitidine therapy was 48%. Among the 18 patients who started azacitidine within 2 months of documented relapse the 6-month survival was 50%. Blast count at time of relapse was not significantly associated with survival (> 1% vs ≤ 1%, HR=1.26, p=0.63), nor was survival after initial treatment with azacitidine affected by longer time intervals prior to first administration (> 28 days vs ≤ 28 days, HR=0.85, p=0.76). There were 12 patients who received gemtuzumab with azacitidine, and the addition of gemtuzumab made no difference in survival (HR with gemtuzumab = 0.81 (0.3-2.1), p=0.66). The 6-month survival with azacitidine is superior to that observed with induction chemotherapy (20%) or WIS (10%). Azacitidine therapy may be superior to standard therapies for recurrent/persistent disease following HCT and warrants further study. Disclosures: No relevant conflicts of interest to declare.

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