DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III-IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD. A wide range of second/third-line agents included cyclosporin, mycophenolate, tacrolimus, imatinib, infliximab and ECP. Relapse of initial malignancy occurred in 37%. Relapse was significantly less frequent in those receiving pre-emptive DLI. Relapse rates were also lower in those with GVHD (31%) than those without GVHD (50%), but this did not reach statistical significance. At 55 months post DLI, 34% of patients had died most commonly from relapse and 22% had on-going GVHD. Although GVHD was an important cause of morbidity post DLI (71%), only 6% died from GVHD. Although most patients develop GVHD post DLI and may require consecutive therapies, mortality from GVHD is infrequent. DLI remains an important option for relapse post transplant and manipulation of the GVT effect needs to be optimised to induce remission without morbidity from GVHD.Bone Marrow Transplantation (2015) 50, 62-67; doi:10.1038/bmt.2014.227; published online 13 October 2014 INTRODUCTION DLI is the only form of adoptive immunotherapy that is in widespread use following haematopoietic SCT (HSCT) in patients with either mixed donor chimerism (pre-emptive) or relapse (therapeutic) to harness the graft-versus-tumour (GVT) effect. The first report of DLI leading to remission of disease following relapse after HSCT was in a patient with CML in 1990.1 Prior to DLI, patients relapsing post HSCT would likely succumb to their disease and a few would receive a second transplant. Following success in CML, DLI was then utilised for other haematological malignancies such as acute leukaemia and myeloma. [2][3][4][5][6] The GVT effect, which is responsible for enabling sustained remission, is also responsible for the most frequent toxicity, GVHD. For this reason, significant pre-existing GVHD is considered a relative contraindication to DLI. There are limited data on the characteristics of GVHD post DLI or response to therapy. The aim of this study was to perform a multicentre study to investigate the type, severity, treatment and response rates of GVHD and DLI schedule.
Introduction: Post transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Treatment has proved difficult and includes dose reduction of immune suppression, combination chemotherapy, surgical excision and radiotherapy. Recently the monoclonal antibody Rituximab, has been added to the therapeutic choice, but how and when to use it is not clear. Previous studies have reported limited success with Rituximab alone plus decreased immune suppression (Choquet et al Blood2003:102:11, 986). We retrospectively analysed 40 patients who developed PTLD post-renal transplant. Methods Patients were evaluated who received a renal transplant between 1981–2000. 30 patients were male and 10 female (median Age 46 years, range 21–70). The median time to development of PTLD was 54 months (range 1m–192m). Diagnostic samples were analysed by immunohistochemistry and clonality assessed by molecular analysis. For patients with monomorphic High grade histology an 18 FDG-PET scan was performed at diagnosis and an interim scan after 2 cycles of therapy (CHOP or CHOP/R, 21 day cycle). Treatment groups received a) no treatment due to rapidly progressive disseminated disease, b) decreased immune suppression alone, c) decreased immune suppression plus combination chemotherapy, d) decreased immune suppression plus single agent rituximab, e) decreased immune suppression plus combination chemo-immunotherapy (CHOP/R, all late B-PTLD > 3 years), or f) surgery (n=1). Results Median Overall survival for all patients was 15 months (range 0.5–96 months). For different patient groups according to treatment, median OS was as follows: For no treatment group (n=5, OS 2.5 months), for decreased immune suppression group (n=8, OS 53.5 months, all less aggressive polymorphic histology), for decreased immune suppression plus chemotherapy (n=16) median OS was 14 months, for the decreased immune suppression group plus single agent Rituximab (n=4) median OS 22months, for the decreased immune suppression group plus chemo immunotherapy (n=6) median OS is 34.5months (range 8–48months) with 6/6 (100%) patients alive and well in CR. No patients treated with CHOP/R suffered any adverse side effects or renal co-morbidity. 10 patients underwent an initial diagnostic PET scan and an interim PET scan .9/10 patients interim PET was negative and 1 patient obtained a PR which become negative at the end of treatment. All patients with a negative interim PET currently remain in CR (100%) at a median follow up of 30 months. Conclusions The treatment of B-PTLD is difficult. Our series of patients now includes long term follow up on patients who either received Rituximab alone plus decreased immune suppression or chemo-immunotherapy plus decreased immune suppression. With a median follow up of 34.5 months, all CHOP/R treated patients are in CR. These results are encouraging and appear to offer significant improvement over previous treatments modalities i.e. chemotherapy only. For PTLD with high-grade histology a negative interim PET scan was highly predictive of prolonged OS and CR status.
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