Graft-Versus-T-Cell Lymphoma Effect

LETTER TO THE EDITOR Graft-versus-T-cell lymphoma effect: a sustained CR after tapering immunosuppressive drugs in a patient with angioimmunoblastic T-cell lymphoma in relapse after allogeneic transplantation

Bone Marrow Transplantation (2015) 50, 304–306; doi:10.1038/ have a place in the therapeutic arsenal after allo-SCT. However, bmt.2014.243; published online 3 November 2014 few data are available on the effect of DLI on relapse after allo- HSCT, especially for lymphomas. Regarding B-cell lymphomas, better responses to DLI are reported in indolent lymphomas than Peripheral T-cell lymphomas form a heterogeneous group of poor- in aggressive lymphoma subtypes, highlighting the complexity of prognosis hematological malignancies representing 10–15% of all the immune reaction. A similar allogeneic effect against auto- lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) is a reactive host lymphocytes has also been suggested in auto- subtype defined by follicular helper T-cell proliferation. AITL carries immune diseases, especially autoimmune cytopenias.7 In Dodero's a particularly poor prognosis. Chemotherapy-based treatment study,8 three CR and three PR cases were obtained after DLI in 12 (usually a CHOP-like regimen) yields a response rate of ~ 60%, but patients with T-cell lymphomas who relapsed after allo-HSCT, but long-term disease-free survival (DFS) only reaches ~ 20%. Kyriakou 5 of them had received salvage chemotherapy before DLI. In et al.1 reported a series of 146 AITL patients treated with another large cohort, patients who received DLI both had a autologous hematopoietic SCT (HSCT): the OS rate at 4 years sustained second CR.2 Coradini3 treated three patients with DLI for was 59% but the 2-year cumulative incidence of relapse was 40%. PD after allo-HSCT, obtaining one PR and one CR. Neither report Indirect evidence points to a graft-versus-lymphoma (GVL) effect mentioned concomitant or prior chemotherapy. Finally, regression after allo-HSCT for peripheral T-cell lymphoma (PTCL; summarized of extranodal relapse after CsA tapering has been reported in two in Table 1). Most chemoresistant patients relapse after auto-SCT, patients.9,10 whereas allo-SCT can provide long-term DFS in a substantial Here, we report the first observation clearly supporting an number of cases. In a recent large study,2 13 patients with stable allogeneic effect on nodal relapse after allo-HSCT for AITL. A disease, progressive disease (PD) or refractory disease before allo- 56-year-old man presented in July 2008 with asthenia, weight loss, transplantation had a CR after allo-HSCT with myeloablative fever, night sweats and polyadenopathy. Blood analyses showed conditioning, with a median 5-year OS of 29%. Similar results were lactate dehydrogenase (LDH) elevation and polyclonal hypergam- obtained after reduced-intensity conditioning allo-SCT in 17 maglobulinemia. Histological analysis of a cervical node biopsy patients who were allografted for relapsed or refractory PTCL.3 specimen showed morphologic and immunophenotypic charac- Another argument in favor of a GVL effect is the poor efficacy of teristics of AITL. Serological tests for HIV and hepatitis C and B T-depleted transplantation: Duarte et al.4 reported 2-year PFS rates viruses were negative. Computed tomography (CT) revealed of 17% after ex vivo T-cell-depleted allo-HSCT and 39% after T-cell- enlarged mediastinal, abdominal and retroperitonal lymph nodes, repleted allo-HSCT. splenomegaly and bilateral pulmonary abnormalities. BM biopsy Interestingly, the occurrence of GVHD was also associated with showed no malignant involvement. Stage IV lymphoma (Ann a better outcome.5,6 Arbor classification) with extranodular involvement was diag- On the basis of the hypothesis that allogeneic donor T cells can nosed. The patient received six cycles of the CHOP regimen eliminate residual recipient malignant lymphoid cells, DLI may combined with alemtuzumab. The disease was chemosensitive.

Table 1. Allogeneic transplantation for T-cell lymphoma: results of recent studies

Histological Conditioning NRM (%) PFS (%) OS (%) Post-transplant Response to DLI at subtype regiment relapse (%) relapse (CR or PR)

Kyriakou AITL:45 25 MAC 25 (1 year) 53 (3 years) 64 (3 years) 20 — et al.6 20 RIC Corradini PTCL:17 17 RIC 6 (2 years) 64 (3 years) 81 (3 years) 15 2/3 et al.3 Le Gouill PTCL:77 57 MAC 33 (1 year) 53 (5 years) 57 (5 years) 17 2/2 et al.2 20 RIC Dodero et al.8 PTCL:52 52 RIC 12 (5 years) 40 (5 years) 50 (5 years) 49 8/12 Duarte et al.4 MF:36 16 MAC 38 (1 year) 22 (3 years) — 33 — Sezary:24 44 RIC 14 (1 year) 39 (3 years) — 42 10/17 25 T-depleted 17 (3 years) — 70 — graft Abbreviations: AITL = angioimmunoblastic T-cell lymphoma; MAC = myeloablative conditioning; MF = mycosis fungoides; NRM = nonrelapse mortality; PTCL = peripheral T-cell lymphoma; RD = refractory disease; RIC = reduced-intensity conditioning. Letter to the Editor 305 a mediastinal nodes (1.5 cm, compared with 4 cm at post-transplant relapse). A third PET/CT scan performed 2 weeks later showed no pathological metabolic activity (Figure 1b). GVHD was successfully controlled with corticosteroids (2 mg/kg) and CsA. The GVHD became chronic, affecting the skin, mucosae and eyes, and requiring low-dose CsA. Corticosteroids were slowly tapered and withdrawn 26 months post transplant. The patient made a good clinical recovery, apart from moderate chronic GVHD. No evidence of disease activity was found on control PET scans 33 months post transplant. This case strongly suggests an allogeneic effect on nodal relapse after allo-HSCT. No chemotherapy or corticosteroids were administered before the response, which was thus induced by CsA tapering and the subsequent occurrence of chronic GVHD. In conclusion, as a ﬁrst-line treatment, both auto- and allo-HSCT seem to provide encouraging results in peripheral T-cell lymphoma, and the available retrospective data do not show a PET/CT scan, day + 100 post transplant clear advantage of one strategy over the other. A prospective b clinical trial is currently addressing this question. Nevertheless, as illustrated by this patient’s case, there is very likely a GVL effect in this setting, suggesting that ‘aggressive’ immunomodulation after allo-HSCT (DLI or early tapering of immunosuppressive drugs) may be warranted for high-risk patients. Allo-HSCT may prove to be a curative treatment for chemoresistant PTCL and for relapsed pTCL after auto-HSCT.

CONFLICT OF INTEREST The authors declare no conﬂict of interest.

ACKNOWLEDGEMENTS Written informed consent (copy available on demand) was obtained from the patient for publication of this case report and accompanying images. PET/CT scan, day +180 post transplant 1 1 1 1 2 a AC Mamez , L Souchet , D Roos-Weil , M Uzunov , AL Brun , Figure 1. ( ) PET scan performed on day +100 post transplant, C Algrin1, V Leblond1 and S Nguyen1 showing an increase in the size and SUV of mediastinal sites. (b) PET 1 ‘ ’ Service d’Hématologie, Hôpital Pitié Salpêtrière, Paris, France and scan performed on day +180 post transplant, showing spontaneous 2 subsidence of abnormal mediastinal metabolic activity, coinciding Service de Radiologie, Hôpital Pitié Salpêtrière, Paris, France with the occurrence of chronic GVHD. E-mail: [email protected]

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