Extracorporeal photopheresis for GVHD prophylaxis after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation: a prospective multicenter phase 2 study

2017 ◽  
Vol 59 (2) ◽  
pp. 372-380 ◽  
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Frederic Garban ◽  
Claude Eric Bulabois ◽  
Ibrahim Yakoub-Agha ◽  
...  
Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2147-2147
Author(s):  
Gregory A. Abel ◽  
Haesook T. Kim ◽  
Philippe Armand ◽  
Corey S. Cutler ◽  
Joseph H. Antin ◽  
...  

Background The National Care Determination for allogeneic hematopoietic stem cell transplantation (allo HSCT) for the treatment of myelodysplastic syndromes (MDS) stated that there is an absence of convincing evidence that allo HSCT improves health outcomes. A prospective data-gathering trial sponsored by the CIBMTR is ongoing; however, until such results are available, retrospective methods specifically comparing older populations are illustrative. Methods We analyzed outcomes for older patients with MDS undergoing HSCT with reduced intensity conditioning (RIC) at the Dana-Farber/BWH with uniform conditioning and graft versus host disease (GVHD) prophylaxis regimens from 2001 to 2011. Patients with CMML were excluded. Those aged 60-65, and those ≥ 66 were compared to assess overall survival (OS), progression free survival (PFS), and other HSCT-related outcomes. Aiming to build a better prognostic score using its significant components, we also assessed the association of the IPSS-R at transplantation as well as each of its components with OS, and fit multivariable Cox regression models with the new prognostic score as well as age. Results We identified 67 patients aged 60 or older who underwent RIC HSCT for MDS. All patients received fludarabine and intravenous busulfan as conditioning, and peripheral blood stem cells. GVHD prophylaxis included tacrolimus/rapamycin +/- MTX. The median age was 64 (60-74) years, and the majority (64%) had unrelated donors. 60% had advanced MDS (IPSS-R high risk or very high risk), 46% had poor risk cytogenetics, and 67% had high or very high disease risk index (DRI). The median age for the 60-65 group was 63; the median age for the ≥ 66 group was 69. We found no significant differences in PFS or OS by age category, as shown below (also see figure): In addition, rates of 6-month grade III-IV GVHD (p=.45) and 2-year incidence of cGVHD (p=0.78) did not significantly differ. The IPSS-R performed only modestly in predicting 4-year OS for this older cohort (p=.20); however, a new 3-level score (including collapsed cytogenetic categories, dichotomous platelet count [ ≥ 50 or < 50], percent blasts in marrow and dichotomous ANC) performed better (p=.008; see figure). In two multivariable models, one that included the IPSS-R and another that included the new score, age was not a significant predictor of OS (p=.78 and .77 respectively). Conclusions Our data suggest that age alone should not limit availability of RIC HSCT for patients with MDS, as older patients in our elderly cohort faired similarly to younger ones with respect to important HSCT-related outcomes. Our new prognostic score, if validated, may be able to help risk-stratify patients. Finally, continued efforts are needed to reduce relapse in high-risk elderly MDS patients. Disclosures: No relevant conflicts of interest to declare.


2008 ◽  
Vol 26 (35) ◽  
pp. 5767-5774 ◽  
Author(s):  
Philippe Armand ◽  
Supriya Gannamaneni ◽  
Haesook T. Kim ◽  
Corey S. Cutler ◽  
Vincent T. Ho ◽  
...  

PurposeInhibitors of the mammalian target of rapamycin (mTOR) kinase have shown clinical activity in several lymphoma subtypes. Sirolimus, an mTOR inhibitor, also has activity in the treatment and prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation (HSCT). We hypothesized that the use of sirolimus for GVHD prophylaxis in patients with lymphoma might lead to improved survival after transplantation through a decreased incidence of disease progression.Patients and MethodsWe retrospectively analyzed 190 patients who underwent transplantation for lymphoma. We compared the outcomes of patients who received sirolimus for GVHD prophylaxis with those of patients who received transplantation with a combination of a calcineurin inhibitor and methotrexate without sirolimus.ResultsOverall survival (OS) after transplantation was significantly superior in the sirolimus group, which was confirmed in multivariable analysis. The benefit was restricted to patients undergoing reduced-intensity conditioning (RIC) HSCT (3-year OS, 66% for sirolimus group v 38% for no-sirolimus group; P = .007; hazard ratio [HR] for mortality in multivariable analysis = 0.5, P = .042). Patients who received sirolimus had a similar incidence of nonrelapse mortality but a decreased incidence of disease progression compared with patients who did not receive sirolimus (3-year cumulative incidence of progression, 42% v 74%, respectively; P < .001; HR for progression in multivariable analysis = 0.4, P = .01). The effect of sirolimus persisted after adjusting for the occurrence of GVHD. No such survival advantage was apparent in a similar comparison of patients who underwent transplantation for diseases other than lymphoma.ConclusionThis study suggests that sirolimus can independently decrease the risk of lymphoma progression after RIC HSCT, paving the way for prospective clinical trials.


2012 ◽  
Vol 40 (11) ◽  
pp. 892-898 ◽  
Author(s):  
Jury L. Shevchenko ◽  
Alexey N. Kuznetsov ◽  
Tatyana I. Ionova ◽  
Vladimir Y. Melnichenko ◽  
Denis A. Fedorenko ◽  
...  

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