Age Does Not Predict Outcomes For Elderly Patients With Myelodysplastic Syndromes Undergoing Hematopoietic Stem Cell Transplantation With Reduced-Intensity Conditioning

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2147-2147
Author(s):  
Gregory A. Abel ◽  
Haesook T. Kim ◽  
Philippe Armand ◽  
Corey S. Cutler ◽  
Joseph H. Antin ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Older Patients ◽  
Prognostic Score ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Very High ◽  
Reduced Intensity

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.

scholarly journals Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis

2013 ◽  
Vol 31 (21) ◽  
pp. 2662-2670 ◽  
Author(s):  
John Koreth ◽  
Joseph Pidala ◽  
Waleska S. Perez ◽  
H. Joachim Deeg ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Life Expectancy ◽  
Stem Cell Transplantation ◽  
Older Patients ◽  
De Novo ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Purpose Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk. Patients and Methods A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q– syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165). Results For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates. Conclusion For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC transplantation offers overall and quality-adjusted survival benefit.

Efficacy of Reduced Intensity Conditioning (RIC) with FLU-BU-ATG and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric ALL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2314-2314 ◽  
Author(s):  
Reggie Duerst ◽  
David Jacobsohn ◽  
William T. Tse ◽  
Morris Kletzel
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Pediatric All ◽  
Very High ◽  
Reduced Intensity

Abstract Reduced Intensity Conditioning (RIC) regimens prior to allogeneic HSCT have gained acceptance in the treatment of adults with myelodysplasia, leukemia and multiple myeloma. RIC reduces the risk for regimen related morbidity and mortality enabling patients with pre-existing medical conditions that would have been precluded from allogeneic HSCT to attempt a curative approach. The resilience of pediatric patients (pts) following high-dose conditioning regimens and the concern that ALL cells are inherently more resistant to a graft-vs-leukemia effect have limited accrual of pediatric ALL pts to RIC protocols despite the potential benefit for reduced long-term morbidity. We report the experience of 10 pediatric ALL pts (6 M, 4 F, median age 9.5 years) treated for recurrent ALL with RIC and allogeneic HSCT. A uniform RIC regimen comprised of fludarabine, 30 mg/m2 for 6 consecutive days (days −10 through −5), followed by intravenous busulfan, 0.8 – 1 mg/kg for 8 doses or targeted AUC 4000 μMol*min for 2 doses (days −5 and −4) and equine ATG, 40 mg/kg or rabbit ATG, 2 mg/kg for 4 days (days −4 through −1) was administered. Pts with prior CNS involvement received whole brain (2400 cGy) and spinal (1800 cGy) irradiation immediately prior to the RIC. Stem cell sources included 7 unrelated donors and 3 matched sibs. 9 of 10 stem cell donations were peripheral blood stem cells (PBSC). The median cell doses infused were 6.5 x 108 MNC/kg and 4.2 x 106 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) alone in 5 patients, CsA and mycophenolate mofetil in 5 pts. Growth factor support was not used. Each of the pts had at least two very high-risk features--prior HSCT (n = 6), CR > 3/refractory disease (8), prior CNS disease (6), Ph+ (2), pre-exisiting neurologic (1) or cardiac (1) dysfunction or aspergillous infection (1). Full donor chimerism was achieved in 9 of 10 with a median time to reach an ANC >500/μl of 16 days (range 11–62) and an unsupported platelet count > 20,000/μl was achieved in 8 of 10 at a median of 25 days (15–67). 2 pts developed Gr IV acute GVHD, 2 of 5 pts surviving more than 100 days developed chronic GVHD. Only 3 patients have relapsed: 1 refractory T-ALL pt recurred day +27 and 2 Ph+ pts had a molecular relapse day +61 and +196. The latter pt is in subsequent continuous molecular remission for over 1 year on imatinib therapy. 6 pts have died, 5 in the first 100 days of HSCT from complications of GVHD (2), relapse (1), pulmonary failure (in 1 pt S/p 3 prior allogeneic HSCT) and PTLD (1). 1 pt succumbed from complications of chronic GVHD day +756. The RIC regimen and supportive care are primarily an outpatient experience. During the first 30 days post HSCT, pts spent an average of only 9 days in hospital (23 of the first 100 days). Despite very high-risk features, 4 of 10 pts survive (3 CCR) at a median of 500 days post HSCT. Thus, RIC and allogeneic HSCT also offers promise for efficacy in pediatric ALL.

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