Predictors of death from chronic graft-versus-host disease after bone marrow transplantation

Wingard, John R.; Piantadosi, Steven; Vogelsang, G. B.; Farmer, ER; Jabs, DA; Levin, L. Stefan; Beschorner, William E.; Cahill, Richard A.; Miller, DF; Harrison, Duane D.

doi:10.1182/blood.v74.4.1428.1428

Cited by 196 publications

(26 citation statements)

References 16 publications

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“…Chronic graft-versus-host disease (GVHD) is a major contributor to post-HCT morbidity and mortality, affecting 40-80% of recipients who survive to day 100 following allogeneic HCT (Socie et al, 1999;Goerner et al, 2002;Lee et al, 2002Lee et al, , 2003. Five-year overall survival rates among those who develop chronic GVHD range from 80% to as low as 35%, dependent upon risk factors such as donor type, overall severity of chronic GVHD, extensive skin involvement, progressive onset of chronic GVHD without prior resolution of acute GVHD and thrombocytopenia (Sullivan et al, 1988;Wingard et al, 1989;Akpek et al, 2003;Arora et al, 2011;Storb et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

et al. 2015

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Summary The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) was designed as a predictor of non-relapse mortality after HCT. Chronic graft-versus-host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT-CI could predict development of chronic GVHD or post-chronic GVHD mortality. We retrospectively analyzed data from 2,909 patients treated at four institutions with allogeneic HCT for malignant and non-malignant hematologic conditions. In Cox regression models adjusted for potential confounders, increasing HCT-CI was not statistically significantly associated with the development of chronic GVHD (hazard ratio [HR]: 1.02, P = 0.34). Yet, the index was associated with an increased risk of non-relapse mortality (HR 1.29, P <0.0001) as well as overall mortality (HR: 1.25, P < .001) following the development of chronic GVHD. The association between HCT-CI and post-chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT-CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.

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Section: Discussionmentioning

confidence: 99%

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

et al. 2015

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“…Several investigators have tried to develop improved prognostic grading scales based on larger numbers of observed patients and with survival as the primary end point. Several studies show that thrombocytopenia (platelet count <100 × 10 9 /l), progressive onset, skin involvement, poor performance status and gastrointestinal (GI) involvement portend a poorer prognosis (Shulman et al , 1980; Wingard et al , 1989; Morton et al , 1997; Akpek et al , 2001a; Lee et al , 2002a; Arora et al , 2003). The Hopkins model stratified patients into risk categories according to the presence or not of extensive skin involvement, thrombocytopenia and progressive‐type onset (Akpek et al , 2001a).…”

Section: Classification Of Chronic Gvhdmentioning

confidence: 99%

Chronic graft versus host disease

2004

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SummaryThe ability to cure increasing numbers of individuals for malignant and non-malignant diseases with the use of stem cell transplantation has resulted in a growing number of long-term survivors with unique medical issues. Chronic graft versus host disease (GvHD) continues to be a significant problem in the allogeneic stem cell transplant setting and, as we continue to use alternative stem cell sources and attempt to modulate the immune system to increase an anti-tumour effect, we will probably see rising numbers of patients with this complication. The capacity to treat this problem and improve both the immediate quality of life as well as long-term effects is imperative and requires the ability of haematologists/oncologists to identify chronic GvHD and its multi-organ system presentations. We describe the risk factors for developing chronic GvHD, its presentation and the current treatment options for both initial therapy and secondary treatment. BackgroundChronic graft versus host disease (GvHD) is the most common non-relapse problem affecting long-term survivors of allogeneic haematopoietic cell transplantation (HCT). Of the 60-70% patients receiving human leucocyte antigen (HLA)-identical sibling marrow grafts or alternative donor marrow grafts who survive beyond day 100 develop chronic GvHD Goerner et al, 2002;Lee et al, 2002a). The incidence of chronic GvHD is lower in children but remains significant. A review of the experience of a single centre, which evaluated patients transplanted for leukaemia using several different regimens for GvHD prophylaxis, had a chronic GvHD rate of 34% (Gustafsson Jernberg et al, 2003). A recent evaluation of GvHD following matched sibling or one antigen mismatched-related transplantation by the Children's Cancer Group, in which GvHD prophylaxis was uniform, reported a chronic GvHD rate of 21AE2% with 7AE3% of the patients with limited disease and the remaining 14% demonstrating extensive disease (Neudorf et al, 2004). These patients received methotrexate for GvHD prophylaxis as per the Seattle protocol until day 100. There remains marked heterogeneity in the GvHD prophylaxis and the stem cell source in the paediatric population making the true estimate of chronic GvHD incidence difficult to quantify.Patients with chronic GvHD report a significantly decreased quality of life (QOL) with a decreased functional status (Syrjala et al, 1993;Duell et al, 1997;Sutherland et al, 1997;Socie et al, 1999). There is minimal data on the life-long complications of chronic GvHD in the paediatric population, including the effects on school performance. Unfortunately, chronic GvHD is becoming a more frequent problem due to the increasing use of alternative donors including haploidentical family members, increasing age limits of transplantation, use of peripheral blood stem cells (PBSC) instead of bone marrow (BM) as the source of the graft, and use of donor lymphocyte infusions (DLI) for treatment of relapse or prophylaxis to prevent relapse in patients at high risk for relapse of their ...

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“…9,12,13,18,19 Importantly, GVHD can often be prevented and treated with immunosuppressive therapy to ensure adequate disease control. 12,13,[20][21][22] Given the association between depression and low medical adherence, 23 it is plausible that pre-HCT depression may affect hospital length of stay during the first 100 days post-HCT as well as the incidence of GVHD.…”

Section: Introductionmentioning

confidence: 99%

Impact of pre‐transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation

El‐Jawahri

Chen

Brazauskas

et al. 2017

Cancer

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Background To evaluate the impact of depression prior to autologous and allogeneic HCT on clinical outcomes post-transplant. Methods We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n=3786) or allogeneic (n=7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment vs. those without pre-HCT depression. Using Cox regression models, we compared OS between patients with or without depression. We compared the number of days-alive-and-out-of-the-hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade II-IV acute and chronic GVHD in allogeneic HCT. Results 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression underwent allogeneic HCT in 2008-2012 were included. Pre-transplant depression was associated with lower OS (HR=1.13, 95%CI1.04-1.23, P=0.004) and higher incidence of grade II-IV acute GVHD (HR=1.25, 95%CI 1.14-1.37, P<0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days alive and out-of-the hospital (Means-Ratio (MR)=0.97, 95%CI0.95-0.99, P=0.004). There were 512 (13.5%) patients with pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR=1.15, 95%CI0.98-1.34, P=0.096), but was associated with fewer days-alive-and-out-of-the-hospital (MR=0.98, 95%CI0.97-0.99, P=0.002). Conclusions Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients, and fewer days-alive-and-out-of-the-hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a vulnerable population at risk for post-transplant complications.

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Predictors of death from chronic graft-versus-host disease after bone marrow transplantation

Cited by 196 publications

References 16 publications

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

Chronic graft versus host disease

Impact of pre‐transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation

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