Chronic graft versus host disease

Abstract

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 ...

Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation

“…For this reason, this grading system, although highly reproducible and useful for clinical decision making as to whether to initiate treatment, provides only limited information on the prognosis of patients. 10,11 Several clinical and biologic features have been identified as prognostically significant in previous studies of cGVHD, including categorization as extensive cGVHD, 9,12 Karnofsky performance status (KPS), 12 thrombocytopenia (o100 000 mm 3 ), 12,13 progressive-type onset of cGVHD, 14 lichenoid histology, 14 and elevated bilirubin. 14 According to recently introduced new clinical grading systems for cGVHD, 10,11 thrombocytopenia, progressive-type onset, and extensive skin GVHD, involving more than 50% of body surface area at the diagnosis of cGVHD, are independent risk factors affecting relapse-free survival.…”

“…The most important factor is the presence of prior aGVHD, which has been repeatedly identified in several studies. [2][3][4][5][6][7] Other factors include older age, diagnosis of chronic myelogenous leukemia, female donor to male recipient, and the use of an unrelated donor. 2,4,6,7 A recent meta-analysis confirmed that use of peripheral blood stem cells significantly increases the risk of cGVHD.…”

The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT

“…cGVHD is thought to be closely associated with aGVHD, but recent studies indicate that besides the time of onset, cGVHD and aGVHD differ both clinically and pathobiologically. 34,35 In addition, aGVHD does not necessarily develop into cGVHD, nor does cGVHD necessarily follow aGVHD. Moreover, cGVHD involves pathogenic autoreactivity in addition to alloreactivity.…”

Patients receiving HLA-haploidentical/partially matched related allo-HSCT can achieve desirable health-related QoL that is comparable to that of patients receiving HLA-identical sibling allo-HSCT

“…3,5,10,12,13,20 Several scholars indicated that use of mismatched or unrelated donors was a risk factor for cGVHD. 20 However, Teshima et al 21 only noted a tendency for increasing cGVHD with increasing HLA disparity, rather than a statistically significant correlation (P ¼ 0.05); other studies found that the occurrence of cGVHD did not differ between patients receiving ISD vs HID/PMRD HSCT, 22,23 which may be due to the usage of ATG in these studies. Several studies observed that the incidence of cGVHD and extensive cGVHD decreased sharply (23 --40% and 23 --26%, respectively) in patients treated with ATG compared with patients treated without ATG.…”