Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul 20;31(21):2662-70.
doi: 10.1200/JCO.2012.46.8652. Epub 2013 Jun 24.

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

Affiliations
Free PMC article

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

John Koreth et al. J Clin Oncol. .
Free PMC article

Abstract

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.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Markov decision model. All patients (stratified by risk state into low/intermediate-1 International Prognostic Scoring System [IPSS; model A] or intermediate-2/high IPSS [model B]) began in the “alive with MDS” state and were able to transition after each 3-month cycle to other health states as indicated. The reduced-intensity conditioning (RIC) transplantation state was transitory, and all patients entering the transplantation state transitioned to another health state by the end of the cycle. MDS, myelodysplastic syndromes.
Fig 2.
Fig 2.
(A) Monte Carlo analysis for low/intermediate-1 International Prognostic Scoring System (IPSS) myelodysplastic syndromes (MDS). Simulated Kaplan-Meier survival plots (n = 10,000; with log-rank P value) are indicated for the modeled 10-year time period, comparing a strategy of early reduced-intensity conditioning (RIC) transplantation (blue line) versus no early RIC transplantation (gold line). The results graphically indicate survival benefit of the nontransplantation strategy in low/intermediate-1 IPSS MDS quality-adjusted life expectancy (QALE): two-way sensitivity analysis. Two-way sensitivity analysis plot for the utilities of the Markov states “alive after RIC transplantation” and “alive with MDS without RIC transplantation” is shown. The gold area indicates the range in which nontransplantation therapy produces superior QALE. The blue area indicates the range in which RIC transplantation produces superior QALE. The red square indicates the plausible range of quality of life (QoL) for “alive with low/intermediate-1 IPSS MDS” and for “alive after RIC transplantation” and does not cross the threshold line. This result is interpreted as insensitive, that is, the conclusion regarding benefit does not change within the plausible QoL range. (C) Monte Carlo analysis for intermediate-2/high IPSS MDS. Simulated Kaplan-Meier survival plots (n = 10,000; with log-rank P value) are indicated for the modeled 10-year time period, comparing a strategy of early RIC transplantation (blue line) versus no early RIC transplantation (gold line). The results graphically indicate survival benefit of the early RIC transplantation strategy in intermediate-2/high IPSS MDS. (D) Intermediate-2/high IPSS MDS QALE: two-way sensitivity analysis. Two-way sensitivity plot for the utilities of the Markov states “alive after RIC transplantation” and “alive with MDS without early RIC transplantation” is shown. The gold area indicates the range in which nontransplantation therapy produces superior QALE. The blue area indicates the range in which RIC transplantation produces superior QALE. The red square indicates the plausible range of QoL for “alive with intermediate-2/high IPSS MDS” and for “alive after RIC transplantation” and does not cross the threshold line. This result is interpreted as insensitive, that is, the conclusion regarding benefit does not change within the plausible QoL range. HCT, hematopoietic cell transplantation.
Fig A1.
Fig A1.
Overall survival of nontransplantation cohorts stratified by low/intermediate (int) -1 and int-2/high International Prognostic Scoring System myelodysplastic syndromes.
Fig A2.
Fig A2.
Overall survival of reduced-intensity conditioning transplantation cohorts stratified by low/intermediate (int) -1 and int-2/high International Prognostic Scoring System myelodysplastic syndromes.

Comment in

Similar articles

See all similar articles

Cited by 62 articles

See all "Cited by" articles
Feedback