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Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

ABSTRACT: BACKGROUND:Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. METHODS:This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age???18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). RESULTS:Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P?=?.0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P?

SUBMITTER: Smith SM

PROVIDER: S-EPMC5990449 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

Smith Sonali M SM Godfrey James J Ahn Kwang Woo KW DiGilio Alyssa A Ahmed Sairah S Ahmed Sairah S Agrawal Vaibhav V Bachanova Veronika V Bacher Ulrike U Bashey Asad A Bolaños-Meade Javier J Cairo Mitchell M Chen Andy A Chhabra Saurabh S Copelan Edward E Dahi Parastoo B PB Aljurf Mahmoud M Farooq Umar U Ganguly Siddhartha S Hertzberg Mark M Holmberg Leona L Inwards David D Kanate Abraham S AS Karmali Reem R Kenkre Vaishalee P VP Kharfan-Dabaja Mohamed A MA Klein Andreas A Lazarus Hillard M HM Mei Matthew M Mussetti Alberto A Nishihori Taiga T Ramakrishnan Geethakumari Praveen P Saad Ayman A Savani Bipin N BN Schouten Harry C HC Shah Nirav N Urbano-Ispizua Alvaro A Vij Ravi R Vose Julie J Sureda Anna A Hamadani Mehdi M

Cancer 20180412 12

<h4>Background</h4>Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.<h4>Methods</h4>This study compa ...[more]

PMID: 29645093

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Project description:Patients with follicular lymphoma (FL) typically experience an indolent course; however, the disease is rarely curable with conventional chemotherapy. Autologous hematopoietic cell transplantation (HCT) can extend progression-free survival (PFS) and overall survival (OS), but relapse is the primary cause of failure. Allogeneic HCT confers lower relapse rates due to a graft-versus-lymphoma effect. Reduced-intensity conditioning (RIC) allows the performance of allogeneic HCT with lower toxicity. The Blood and Marrow Transplant Clinical Trials Network conducted a prospective multicenter trial comparing these two strategies in patients with relapsed, chemotherapy-sensitive FL. Patients were assigned to a treatment arm based on the availability of an HLA-matched sibling donor (MSD). Those with an MSD underwent allogeneic HCT (n = 8) with the FCR preparative regimen (fludarabine, cyclophosphamide [Cy], rituximab [RTX]) and received tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Those without an MSD (n = 22) underwent mobilization with Cy, RTX, and filgrastim and received a conditioning regimen of either CBV (Cy, carmustine, Etoposide [VP16]) or total body irradiation with Cy and VP16. Patients undergoing autologous HCT received 4 doses of weekly maintenance RTX (375 mg/m²) starting on day +42 post-HCT. Sixteen patients were in complete remission, 10 patients were in partial remission, and 1 patient had stable disease after salvage therapy and before HCT. Median follow-up was 36 months (range, 1-51 months). OS was 73% in autologous HCT versus 100% in allogeneic HCT, and PFS was 63% in autologous HCT versus 86% in allogeneic HCT. No patient had grade II-IV acute GVHD; two patients developed extensive chronic GVHD. Three autologous recipients died from nonrelapse causes. This trial closed early because of slow accrual. We show that the FCR regimen is well tolerated, and that both allogeneic and autologous HCT result in promising 3-year OS and PFS in patients with relapsed FL.

Project description:Large, multicenter studies comparing commonly used reduced-intensity conditioning (RIC) approaches in follicular lymphoma (FL) have not been performed. Using the Center for International Blood and Marrow Transplant Research database, we report the outcomes of the 2 most commonly used RIC approaches, fludarabine and busulfan (Flu/Bu) versus fludarabine, cyclophosphamide, and rituximab (FCR) in FL patients. We evaluated 200 FL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who received RIC with either Flu/Bu (n = 98) or FCR (n = 102) during 2008 to 2014. All patients received peripheral blood grafts, and graft-versus-host disease (GVHD) prophylaxis was limited to calcineurin inhibitor-based approaches. Median follow-up of survivors in the Flu/Bu and FCR groups was 48 months and 46 months, respectively. On univariate analysis in the Flu/Bu and FCR groups, the 3-year rates of nonrelapse mortality (11% versus 11%, P = .94), relapse/progression (18% versus 15%, P = .54), progression-free survival (PFS) (71% versus 74%, P = .65), and overall survival (OS) (73% versus 81%, P = .18) were not significantly different. On multivariate analysis no difference was seen between the FCR and Flu/Bu cohorts in terms of grades II to IV (relative risk [RR], 1.06; 95% confidence interval [CI], .59 to 1.93; P = .84) or grades III to IV (RR, 1.18; 95% CI, .47 to 2.99; P = .72) acute GVHD, nonrelapse mortality (RR, .83; 95% CI, .38 to 1.82; P = .64), relapse/progression (RR, .99; 95% CI, .49 to 1.98; P = .97), PFS (RR, .92; 95% CI, .55 to 1.54; P = .76), or OS (RR, .70; 95% CI, .40 to 1.23; P = .21) risk. However, RIC with FCR was associated with a significantly reduced chronic GVHD risk (RR, .52; 95% CI, .36 to .77; P = .001). RIC with either Flu/Bu or FCR in patients with FL undergoing allo-HCT provides excellent 3-year OS, with acceptable rates of nonrelapse mortality. FCR-based conditioning was associated with a lower risk of chronic GVHD.

Dataset Information

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

Publications

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

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