Delayed Complications After Hematopoietic Cell Transplantation

Flowers, Mary E.D.; Deeg, H. Joachim

doi:10.1002/9780470987070.ch69

Cited by 14 publications

(9 citation statements)

References 165 publications

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“…In addition, 4 case patients had PUVA skin irradiation and 2 case patients had limited field radiation for GVHD. Two of the 9 control patients with AZA-CSP-steroids had other chronic drug therapy (cyclophosphamide [1], thalidomide [2]), and 2 had PUVA skin irradiation. All but 1 patient (control) in the AZA-CSP-steroids group had steroids for chronic GVHD therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The success rate has improved progressively, and some surviving patients have now been followed up for more than 3 decades. 1 One important complication among transplantation survivors is the development of new (secondary) malignancies, particularly solid tumors [2][3][4][5][6][7][8][9][10] and posttransplantation lymphoproliferative disorders. 3,8,11,12 Previous studies report that transplant recipients who develop chronic graft-versus-host disease (GVHD) are at especially high risk for squamous-cell carcinoma (SCC) of the oral cavity and skin, 6,7,9,10,13,14 with more aggressive behavior noted for some of these tumors.…”

Section: Introductionmentioning

confidence: 99%

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Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study

Curtis

Metayer

Rizzo

et al. 2005

Blood

283

225

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Previous studies of recipients of hematopoietic stem-cell transplants suggest that graft-versus-host disease (GVHD) and its therapy may increase the risk for solid cancers, particularly squamous-cell carcinomas (SCCs) of the buccal cavity and skin. However, the importance and magnitude of these associations are not well characterized. We conducted a casecontrol study of 183 patients with posttransplantation solid cancers (58 SCCs, 125 non-SCCs) and 501 matched control patients within a cohort of 24 011 patients who underwent hematopoietic stem-cell transplantation (HSCT) at 215 centers worldwide. Our results showed that chronic GVHD and its therapy were strongly related to the risk for SCC, whereas no increase in risk was found for non-SCCs. Major risk factors for the development of SCC were long duration of chronic GVHD therapy (P < .001); use of azathioprine, particularly when combined with cyclosporine and steroids (P < .001); and severe chronic GVHD (P ‫؍‬ .004). Given that most patients who received prolonged immunosuppressive therapy and those with severe chronic GVHD were also treated with azathioprine, the independent effects of these factors could not be evaluated. Additional analyses determined that prolonged immunosuppressive therapy and azathioprine use were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement for strategies to prevent chronic GVHD and for the development of more effective and less carcinogenic treatment regimens for patients with moderate or severe chronic GVHD. Our results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both. (Blood. 2005; 105:3802-3811)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study

Curtis

Metayer

Rizzo

et al. 2005

Blood

283

225

View full text Add to dashboard Cite

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“…21,22 The current cohort was at a 15-fold increased risk of late deaths due to pulmonary dysfunction compared with the general population, again emphasizing the need for preventive measures, such as limiting cumulative therapeutic exposure to agents with potential pulmonary toxicity, early and aggressive interventions in patients with pulmonary compromise, and caution against tobacco use in this vulnerable population.…”

mentioning

confidence: 99%

Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study

Bhatia

Francisco

Carter

et al. 2007

Blood

496

377

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We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE ‫؍‬ 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio ‫؍‬ 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapserelated mortality was increased among patients older than 18 years at HCT (

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“…We used an established four-point scale in which manifestations were scored as absent, as causing no functional impairment, as causing functional impairment without disability, or as causing disability. 15 Complete resolution at any site was defined as disappearance of GVHD manifestations, while changes in the score for each organ were classified as improvement or progression when manifestations were still present at the end of follow-up.…”

Section: Betweenmentioning

confidence: 99%

Safety and potential efficacy of low-dose methotrexate for treatment of chronic graft-versus-host disease

Giaccone

Martin

Carpenter

et al. 2005

Bone Marrow Transplant

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Summary:Low-dose methotrexate (MTX) is widely used in autoimmune diseases because of its anti-inflammatory activity. We report here the results of a retrospective study to review the outcomes of low-dose MTX used for treatment of refractory chronic graft-versus-host disease GVHD, with the goal of reducing the amount of prednisone needed to control the disease. In all, 14 patients with refractory chronic GVHD received MTX at a dose of 7.5 mg/m 2 / weekly for 3-50 weeks. Eleven patients had skin involvement, often with scleroderma or fasciitis. The median duration of chronic GVHD at the start of MTX was 38 (range 1-135) months. In this retrospective review, we found no grade 3-4 toxicities, and none of the patients needed blood transfusion or growth factors. In 10 patients (71%), GVHD could be adequately controlled with prednisone at doses below 1 mg/kg every other day without the addition of other agents. Four patients decreased the amount of concomitant immunosuppressive treatment, five continued with the same regimen, four required an increase in immunosuppressive treatment, and one decided to discontinue all treatment. From this preliminary analysis, MTX appears to be a well-tolerated, inexpensive and possibly steroid-sparing agent that is worthy of further evaluation in prospective trials for treatment of chronic GVHD.

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Delayed Complications After Hematopoietic Cell Transplantation

Cited by 14 publications

References 165 publications

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study

Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study

Safety and potential efficacy of low-dose methotrexate for treatment of chronic graft-versus-host disease

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