Beneficial effect of intravenous lidocaine in cutaneous chronic graft-versus-host disease secondary to donor lymphocyte infusion

Abstract

Summary:We report two cases of refractory chronic graft-versushost disease after donor lymphocyte infusions in which the skin lesions improved dramatically with the use of intravenous pulses of lidocaine. This form of therapy has been used successfully for the cutaneous involvement of scleroderma and may have vasodilator and anti-inflammatory effects. Bone Marrow Transplantation (2001) 28, 97-99. Keywords: chronic GVHD; lidocaine; donor lymphocyte infusion Donor lymphocyte infusion (DLI) is a very promising immunotherapeutic modality of treatment for relapse of malignancy after hematopoietic stem cell transplantation (HSCT) (reviewed in Ref. 1). However, it is associated with significant morbidity and mortality due to marrow aplasia and graft-versus-host disease (GVHD). In a survey of 140 patients treated with DLI for relapse of a variety of malignant diseases in 25 North American centers 75 of 125 (60%) evaluable patients developed acute GVHD (28 with grades III or IV) and 51 out of 84 (61%) developed chronic GVHD (24 with limited and 27 with extensive forms). 2 In another series of 22 patients with chronic myelogenous leukemia, nine (41%) developed chronic GVHD (five limited, four extensive forms). 3 In the first study there was a correlation between clinical response to DLI and development of acute and chronic GVHD, while in the latter one low doses of DLI could induce a graft-versus-leukemia effect without GVHD.Chronic GVHD associated with allogeneic HSCT or DLI seems to have a similar clinical picture 4 and may cause significant disability and deterioration of quality of life, in part because of sclerodermatous skin changes leading to severe contractures. 5 These lesions are poorly responsive to conventional immunosuppression or to alternative therapies for GVHD such as thalidomide, mycophenolate mofetil and tacrolimus, etretinate, PUVA (psoralen plus ultraviolet irradiation) and extracorporeal phototherapy. Spontaneously occurring systemic sclerosis shares the autoimmune pathophysiology and poor treatment response with chronic GVHD 6 and local anesthetics were one of many treatments attempted for the skin manifestations of systemic sclerosis. 7 We report here two cases of sclerodermatous cutaneous chronic GVHD after DLI, which responded dramatically to intravenous administration of lidocaine. Case reports Patient 1The first patient, an 11-year-old boy, received an HLAidentical bone marrow transplantation donated by his sister at the University Hospital of the School of Medicine of Ribeirão Preto, Brazil in September 1995 for an acute biphenotypic leukemia in first complete remission. The conditioning regimen was busulfan 16 mg/kg and cyclophosphamide 120 mg/kg and GVHD prophylaxis was methotrexate plus cyclosporine. The early post-transplant course was uneventful without acute GVHD and with establishment of full donor chimerism (100% XX). At day +530 post-transplant hematologic relapse was detected in the bone marrow (17% blasts). An infusion of donor peripheral blood lymphocytes containing 1.13 × 10 8 T c...

Acute severe form of lichenoid graft‐versus‐host disease after donor lymphocyte infusions

“…In both cases with hyperacute GVHD, cutaneous lesions rapidly evolved from an acute to a lichenoid clinical pattern and the histologic examination showed features of both acute and lichenoid GVHD. Other cases of chronic GVHD after ILD have been reported, 5–7 but the type or the extension of the skin lesions is usually not described. The finding that response to DLI is not always associated with acute or chronic GVHD suggests that the graft‐versus‐leukaemia effect may be independent from the clinical development of GVHD 8,9 .…”

Cutaneous Graft-Versus-Host Disease

“…Sekonder tedavilerde talidomid, PUVA, UVA1, UVB, ekstrakorporeal fotokemoterapi, mikofenolat mofetil, etretinat, hidroksiklorakin, intravenöz lidokain, rituksimab ve total lenfoid ışınlama ile başarılı sonuçlar alındığı bildirilmektedir (24,26,33,(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68).…”

Treatment of refractory sclerodermatous chronic graft-versus-host disease with intravenous lidocaine infusions

“…3 A case report described rapid improvement of symptoms and skin lesions in two patients with refractory sclerodermatous cGVHD treated with lidocaine infusions. 4 At our center, the use of IV lidocaine in patients with sclerotic cGVHD has been motivated by continued dependence on high doses of glucocorticoids and the lack of effective alternatives. We report a retrospective series of eight patients treated with IV lidocaine to expand on the current knowledge of this treatment for refractory sclerotic cGVHD.…”

“…We report a retrospective series of eight patients treated with IV lidocaine to expand on the current knowledge of this treatment for refractory sclerotic cGVHD. Between January 2005 and December 2007, we identified eight patients with sclerotic cGVHD treated with lidocaine infusions at doses of 400 mg (diluted in 250 mL of normal saline) over 3.5 h for 5 consecutive days every month (one cycle), 4 for a minimum of three cycles. All patients had cGVHD refractory to glucocorticoids and calcineurin inhibitors, and had previously received three or more lines of therapy.…”