Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective.

The efficacy and safety of CD52 antibody alemtuzumab to treat severe acute GVHD in 18 consecutive patients refractory to standard high-dose corticosteroid therapy is reported. Patients (age range 13-68 years) had developed acute GVHD grade III and IV with gut and/or liver involvement after stem cell transplantation from family donors (n= 7) or HLA-matched unrelated donors (n=11), including five donors with one or two HLA mismatches. Initially, in three patients, start doses of alemtuzumab in the range of 70-80 mg were applied and repeated after 3 to 4 weeks. Impressive responses were seen, but virus reactivation and bacterial infections were frequent. In an attempt to reduce this complication, the next nine patients received a reduced starting dose of 20-33 mg, and the last six patients received 3-13 mg repeated every 2-3 weeks. Seventeen of 18 patients responded to alemtuzumab, six patients are alive with a median follow-up of 108 weeks. Chronic GVHD was observed frequently. Although pronounced lymphocyte depletion requiring close monitoring for signs of infections seems inevitable for efficacy, alemtuzumab given in moderate doses has a substantial activity not only in intestinal but also in severe acute GVHD of the liver.

Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients.

In this multicenter study, 30 patients undergoing matched related or unrelated allogeneic stem-cell transplantation for leukemia were treated with palifermin, and retrospectively compared to a matched control group. Palifermin recipients transplanted with an unrelated donor showed a significant reduction of severity, incidence and duration of oral mucositis WHO grades 2-4. In addition, in the palifermin group the use of opioid analgesics and the duration of total parenteral nutrition decreased, whether stem cells were used from matched related or unrelated donors. No beneficial influence of palifermin on the incidence and severity of acute GVHD (aGVHD) was apparent. The incidence and duration of febrile neutropenia, documented infections, hematopoietic recovery or overall survival remained unchanged. The most common adverse effects included rash or erythema, generally mild and transient in appearance. Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas--regardless of donor status--no effect on the incidence and severity of aGVHD was seen.

Triple antifungal therapy for severe systemic candidiasis allowed performance of allogeneic stem cell transplantation.

Systemic candidiasis is a rare but life threatening complication in immunosuppressed patients undergoing allogeneic SCT. Combination of new antifungal agents may improve outcome in this patient population. Here, triple anti-mycotic therapy is described in an relapsed ALL patient in urgent need of allogeneic bone marrow transplantation. The patient with T-cell acute lymphoblastic leukemia of thymic differentiation achieved remission after treatment according to the German ALL protocol 07/03. Two months after the consolidation therapy relapse occurred requiring high dose chemotherapy with allogeneic stem cell transplantation. One day after start of the conditioning regimen the patient showed skin manifestations typical for septic mycosis and blood cultures became positive for Candida krusei while on fluconazole prophylaxis. Because of the limited sensibility of fluconazole resistant candida species to liposomal amphotericin B and the high mortality rate in patients with systemic candidiasis, voriconazole was added immediately to liposomal amphotericin B. Since fever did not resolve and the conditioning therapy for allogeneic transplantation was not yet completed caspofungin was added. Skin manifestation responded to this triple anti-mycotic combination and peripheral blood stem cells from an unrelated donor were transplanted. With the triple antifungal therapy the patient finally became afebrile, skin manifestations showed complete resolution and blood cultures became negative. Three months after the onset of systemic candidiasis the patient was fully active with no signs of fungal infection and in haematological and molecular remission. Mycotic sepsis at the start of myeloablative conditioning therapy in heavily pretreated acute leukemia patients is usually considered as not allowing successful allogeneic transplantation. Thus this case demonstrates, that allogeneic stem cell transplantation is feasible in patients presenting with systemic candidiasis if combined antifungal therapy with liposomal amphotericin B, caspofungin and voriconazole is given.

Successful autologous stem cell transplantation in a severely immunocompromised patient with relapsed AIDS-related B-cell lymphoma.

There is now evidence that the tolerability and response to systemic chemotherapy in HIV-infected patients with AIDS-related lymphoma (ARL) is significantly improved by highly active antiretroviral therapy. Here we report an severely immunocompromised AIDS patient with recurrent ARL who was successfully treated with autologous stem cell transplantation (ASCT). We also review the current literature of ASCT in HIV-infected patients.