Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul 14;118(2):456-63.
doi: 10.1182/blood-2011-01-330217. Epub 2011 Jun 1.

Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Yoshihiro Inamoto  1 , Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Edus H Warren, H Joachim Deeg, Rainer F Storb, Frederick R Appelbaum, Barry E Storer, Paul J Martin
Affiliations

Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Yoshihiro Inamoto et al. Blood. .

Abstract

This study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.

PubMed Disclaimer

Figures

Figure 1
Figure 1
GVHD and immunosuppressive treatment conditions used for the time-varying analysis. Patients transit from one condition to another in the direction of an arrow at the onset of acute or NIH chronic GVHD, and at the discontinuation of immunosuppressive treatment. (A) GVHD conditions. (B) GVHD and IST conditions.
Figure 2
Figure 2
Rates of recurrent malignancy, and risk of early and late recurrent malignancy according to GVHD condition. (A) Relapse rates were calculated within sequential 90-day intervals for patients without GVHD shown in green, for patients with grades II-IV GVHD without chronic GVHD shown in blue, and for patients with NIH chronic GVHD shown in red. Small symbols represent the actual relapse rates for each 90-day interval. The smoothed rates were plotted as curves for each condition. Low event rates account for large variations between sequential intervals after 36 months. (B-C) Risk of early and late recurrent malignancy according to GVHD condition. *Number of patients at risk in the condition at any time during the period of analysis. †Hazard ratios were adjusted for disease, risk category, and total body irradiation.
Figure 3
Figure 3
Rates of overall mortality and risk of early and late overall mortality according to GVHD condition. (A) Mortality rates were calculated within sequential 90-day intervals for patients without GVHD shown in green, for patients with grades II-IV GVHD without chronic GVHD shown in blue, and for patients with NIH chronic GVHD shown in red. Small symbols represent the actual mortality rates for each 90-day interval. The smoothed rates were plotted as curves for each condition. (B-C) Risk of early and late overall mortality according to GVHD condition. *Number of patients at risk in the condition at any time during the period of analysis. †Hazard ratios were adjusted for disease, risk category, total body irradiation, age of the patient at HCT, donor/recipient sex, donor type, HLA-mismatch, source of stem cells, GVHD prophylaxis, and CMV serologic status.
Figure 4
Figure 4
Rates of recurrent malignancy and risk of early and late recurrent malignancy according to GVHD and immunosuppressive treatment conditions. (A) Results are shown as rates per patient-year during successive 90-day intervals after transplantation. Small symbols represent the actual relapse rates for each 90-day interval. The smoothed rates were plotted as curves for each condition defined by the history of GVHD and continuation or discontinuation of IST. Plots were not illustrated for patients without GVHD who continued IST beyond 12 months because of insufficient sample size. (B-C) Risk of early and late recurrent malignancy according to GVHD and immunosuppressive treatment conditions. *Number of patients at risk in the condition at any time during the period of analysis. †Hazard ratios were adjusted for disease, risk category, and total body irradiation. ‡Effects of discontinued IST were not analyzed beyond 18 months in patients without GVHD, because the reference group was too small.
See this image and copyright information in PMC

Comment in

  • Hematology: Preventing relapse.
    Villanueva MT. Villanueva MT. Nat Rev Clin Oncol. 2011 Jun 28;8(8):448. doi: 10.1038/nrclinonc.2011.99. Nat Rev Clin Oncol. 2011. PMID: 21709697 No abstract available.

References

    1. Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001;411(6835):385–389. - PubMed
    1. Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091–2101. - PMC - PubMed
    1. Socie G, Stone JV, Wingard JR, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med. 1999;341(1):14–21. - PubMed
    1. Martin PJ, Counts GW, Jr, Appelbaum FR, et al. Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol. 2010;28(6):1011–1016. - PMC - PubMed
    1. Miller JS, Warren EH, van den Brink MR, et al. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Biology Underlying Recurrence of Malignant Disease Following Allogeneic HSCT: graft-versus-tumor/leukemia reaction. Biol Blood Marrow Transplant. 2010;16(5):565–586. - PMC - PubMed

Publication types

MeSH terms

Substances