scholarly journals Is hematopoietic cell transplantation still a valid option for mantle cell lymphoma in first remission in the chemoimmunotherapy-era?

2013 ◽  
Vol 48 (12) ◽  
pp. 1489-1496 ◽  
Author(s):  
L Chaudhary ◽  
M A Kharfan-Dabaja ◽  
P Hari ◽  
M Hamadani
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cell Lymphoma ◽  
Hematopoietic Cell ◽  
Mantle Cell ◽  
First Remission

Specific Features Identify Patients with Relapsed/Refractory Mantle Cell Lymphoma Benefitting From Autologous Hematopoietic Cell Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3082-3082
Author(s):  
Ryan D. Cassaday ◽  
Katherine A. Guthrie ◽  
Lihua E. Budde ◽  
Leslie Thompson ◽  
Brian G. Till ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Cell Lymphoma ◽  
Hematopoietic Cell ◽  
Predictive Score ◽  
P Values ◽  
Mantle Cell ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Abstract 3082 Background: High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto HCT) has been shown to improve outcomes in mantle cell lymphoma (MCL) when used in first remission. In contrast, most series evaluating HDT and auto HCT when used for relapsed/refractory (rel/ref) disease suggest that the outcomes are typically poor. Such data have broadly limited the use of HDT and auto HCT in this setting, though the question of a potential benefit of this approach in a subset of these patients has never been addressed. We, thus, hypothesized that certain factors could be identified to predict which patents with rel/ref MCL would experience a favorable outcome after auto HCT. Methods: Records from consecutive pts older than 18 years with a confirmed diagnosis (dx) of MCL receiving HDT and auto HCT between April 1996 and February 2011 at our center were reviewed. Pts who received auto HCT for either second or later remission or for primary refractory disease were identified while excluding those who received a planned tandem auto-allogeneic HCT. Characteristics both at dx and at the time of pre-HCT work-up were recorded. The statistical significance of differences in event rates was evaluated with the proportional hazards regression model. Reported p-values are based on the Wald statistic, and two-sided p-values less than 0.05 were considered statistically significant. Kaplan-Meier (K-M) curves were used to estimate the probabilities of overall and progression-free survival (OS and PFS, respectively). Results: From a cohort of 165 pts, 68 (41%) met the prespecified definition of rel/ref MCL. In this subgroup, the median PFS was 14 months and the median OS was 36 months. The median age at the time of auto HCT was 58 years (range 41–70), and the median number of treatments pre-HDT was 2 (range 1–6). There were 9 pts (13%) with blastoid histology, and 18 patients (26%) had B symptoms (sx) at the time of dx. The median time from dx to auto HCT was 25 months (range 4–183). Pretransplant disease status included CR = 15 (22%), PR = 42 (62%), and chemorefractory or untested relapse = 11 (16%). Pretransplant simplified MIPI scores based on data obtained prior to HDT (sMIPI-Auto) were as follows: ≤ 2 in 26 pts (38%), 3 in 28 pts (41%), and ≥ 4 in 14 pts (21%). Three factors were identified as independent predictors of worse OS and PFS in multivariable models: 1. higher sMIPI-Auto (HR 2.0 for OS, p = 0.001; HR 3.1 for PFS, p < 0.001), 2. presence of B sx (HR 2.5 for OS, p = 0.009; HR 2.6 for PFS, p = 0.005), and 3. lower remission quotient (RQ), calculated by dividing the time in months from diagnosis to auto HCT by the number of prior treatments (HR 1.8 for OS, p = 0.002; HR 1.4 for PFS, p = 0.01). The estimated linear predictors from this multivariable model allowed formulation of a predictive score for OS and PFS, which defined a subset of 23 pts (34%) with relatively low risk of death and/or progression having at least 2 favorable features from the above analysis (see Figure, Score 1). Favorable groups specifically included: 1) sMIPI-Auto of ≤ 2 and no B sx, with a RQ ≥ 5, 2) sMIPI-Auto of ≤ 2, presence of B sx, and a RQ of ≥ 14, and 3) sMIPI-Auto of 3, no B sx, and a RQ of ≥ 14. Pts not meeting one of these sets of criteria, particularly those with either a sMIPI-Auto of ≥ 4 or a RQ of < 5 (independent of the other factors), were predicted to do poorly (see Figure, Scores 2 and 3). The K-M 3-yr estimates for PFS were 66% (95% CI 41 – 82%) for Score 1, 23% (95% CI 9 – 40%) for Score 2, and 24% (95% CI 8 – 45%) for Score 3; the K-M 3-yr estimates for OS were 80% (95% CI 54 – 92%) for Score 1, 43% (95% CI 22 – 62%) for Score 2, and 29% (95% CI 11 – 49%) for Score 3. Conclusions: These data identify 3 simple factors (sMIPI-Auto, B symptoms, and high RQ) that can be used to distinguish MCL patients who may experience prolonged OS and PFS after auto HCT used for the treatment of rel/ref disease. In contrast to studies to date, our detailed analysis of this specific population could be used to provide another effective therapeutic option for up to one third of patients with rel/ref MCL, though independent validation of these results is required. Disclosures: Holmberg: Sanofi: Research Funding; Seattle Genetics: Research Funding; Merck: Research Funding; Otsuka: Research Funding; Millenium: Research Funding.

Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3535-3542 ◽  
Author(s):  
Michael B. Maris ◽  
Brenda M. Sandmaier ◽  
Barry E. Storer ◽  
Thomas Chauncey ◽  
Monic Jain Stuart ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Cell Lymphoma ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Mantle Cell ◽  
Total Body ◽  
Autologous Hct

We carried out HLA-matched related (n = 16) and unrelated (n = 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n = 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses.

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