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 ...

A B S T R A C T PurposeTherapy for patients with chronic graft-versus-host disease (cGVHD) is based on prolonged immunosuppression with corticosteroids. There is no standard therapy for patients whose cGVHD does not resolve with corticosteroid treatment. Pentostatin, a potent inhibitor of adenosine deaminase, has activity in acute GVHD. We examined the toxicity and efficacy of pentostatin in a prospective phase II trial in corticosteroid-refractory cGVHD. Patients and MethodsPatients of any age were eligible. Patients received pentostatin 4 mg/m 2 intravenously every 2 weeks for 12 doses, and continued therapy as long as benefit was documented. Corticosteroid taper was begun after three doses of pentostatin. Responses were graded in real time in the skin, mouth, and liver using objective response criteria. ResultsFifty-eight heavily pretreated (median, four prior regimens) patients (median age, 33 years) were enrolled. Results are shown as an intent-to-treat analysis. Of the 58 patients, a total of 32 (55%; 95% CI, 42% to 68%) had an objective response, as evaluated by use of a new grading scale. Infection was the most significant toxicity, with 11 grade 3 to 4 infectious events. The survival at 1 and 2 years was 78% (95% CI, 64% to 86%) and 70% (95% CI, 57% to 80%), with cGVHD with/without infection accounting for the majority of deaths. ConclusionPentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD.