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We report three patients with lethal forms of acute GVHD in whom all biopsy specimens showed a striking preponderance of macrophages in the inflammatory infiltrate with production of TNF-alpha. The role of the macrophage/TNF-alpha axis in human acute GVHD is examined and the existence of primary macrophagic forms of GVHD is discussed.

We report on seven adult leukemic patients who were autografted in spite of a prior history of invasive pulmonary aspergillosis (IPA). Their median age was 41 years (range: 19-61); six patients were male and one female. All seven had acute myeloblastic leukemia (AML) and underwent an autologous marrow transplantation (ABMT) with a marrow purged in vitro by mafosfamide. IPA was suspected prior to ABMT on clinical and radiological features. CT scan confirmed nodular infiltrates and cavitations in six cases. Microbiological documentation consisted of: identification of the fungus from bronchoalveolar lavage: one case, positive antigenemia: one case, positive antibodies: two cases. Prior ABMT patients received amphotericin B for a median total dose of 1915 mg (range: 970-3300). No patient underwent surgery. The median time from diagnosis of IPA to ABMT was 7.3 months (range: 3-10). During ABMT all patients received prophylactic amphotericin B and itraconazole. No patient died from toxicity and no IPA reactivation was observed in any patients. Post-graft, itraconazole was kept on for a median of 3 months (range: 3-5). This study demonstrates that IPA occurring during the management of AML patients is not necessarily a contraindication to subsequent ABMT.

A systematic survey of human cytomegalovirus (CMV) was performed in 29 allogeneic bone marrow transplant (BMT) recipients. At day 100 a lip biopsy was performed and histological grading according to Sale's score was compared with the immunohistochemical detection of the immediate early protein IE2 of HCMV. In 10 patients without chronic graft-versus-host disease (GVHD), 3 had lip biopsy grade 1, 7 had grade 0 Sale's score and in 19 patients with chronic GVHD, 11 had grade 2, 1 had grade 1 and 7 had grade 0. On the same lip biopsies, we found IE2 protein in 8 of the 19 patients with chronic GVHD. None of the lip biopsies from patients without chronic GVHD expressed the protein, suggesting that HCMV expression is strongly associated with chronic GVHD and Sale's grade 2. To conclude, in our group of patients with a risk for HCMV infection, detection of the protein IE2 was a good predictive criterion of chronic GVHD with a sensitivity of 61% and a specificity of 100%.

This report describes an 18-year-old man with disseminated malignant histiocytosis (MH). The patient initially attained complete remission (CR1) with conventional chemotherapy and then relapsed 14 months later. In second complete remission (CR2) 2 years and 8 months after initial diagnosis, an autologous bone marrow transplantation (ABMT) was undertaken following conditioning with the BEAM regimen. Bone marrow collected in CR2 was incubated with mafosfamide at a dose adjusted to the individual sensitivity of normal CFU-GM according to our current protocol. At the time of writing, 4 years post-transplant, this patient remains disease free. This is the first report of ABMT with marrow treated in vitro by mafosfamide in MH.