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Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

Summary:More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome. Bone Marrow Transplantation (2000) 25, 969-973.

Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post-BMT by assessing T- cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by e or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow-up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR- ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T-cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML.

Summary:11%. 9-11 It occurs more frequently in patients with the M5 FAB subtype and in infants with AML, the incidences being 31 and 46%, respectively. 12-13 Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML). Little information is availableFew studies have evaluated the outcome of patients with LC. The largest published series describes 18 patients with regarding its prognostic influence on post-transplant outcome. In our institution, 202 patients with AML AML and LC who were treated with conventional therapy and who experienced a high incidence of serial skin received an allogeneic HLA-identical marrow transplant from related donors between March 1982 and January relapses, suggesting that skin could provide a sanctuary site for leukemic cells. 14 While patients with acute myeloblastic 1994. Thirteen patients had prior leukemic involvement of the skin (leukemia cutis or LC group) while 189 or lymphoblastic leukemia with prior involvement of extramedullary sites such as CNS or testis treated with BMT patients did not (non-LC group). There was a higher incidence of patients with the M4-M5 FAB subtypes in have been reported to have an increased risk of extramedullary relapse post-transplantation, 15,16 the outcome of the LC group (83%) as compared to the non-LC group (33%). In addition, the percentage of patients transpatients with a history of LC treated with marrow transplantation has not been described previously. planted in relapse was also higher in the LC group (69 vs 15%). While there were no differences observed inWe report a single institution retrospective analysis of 13 patients with AML and LC who underwent allogeneic the rates of relapse post-transplant in the LC and non-LC groups when matched for stage of disease at trans-BMT at Memorial Sloan-Kettering Cancer Center (MSKCC). The overall relapse rates and sites of relapse plant, the sites of relapse differed markedly. Five of six relapses in the LC group involved extramedullary sites that occurred in this group were compared with those observed in 189 consecutive patients with AML without as compared to only six of 38 relapses in the non-LC group (P = 0.002), with a 6-year probability of extramed-LC who were treated with allogeneic BMT during the same time period. ullary relapse of 38.5% in the LC group as compared to 3.9% in the non-LC group. This increased probability of extramedullary relapse was independent of the FAB morphology (50 vs 2% for patients with the M4-M5 subPatients and methods types in the LC and the non-LC group respectively) and of disease status at the time of transplant. Moreover, Patient groups were drawn from a series of 202 consecutive adults and children who received HLA-matched related only three relapses post-transplant involved the skin, all of which were in the LC group, with a probability of bone marrow transplants for the treatment of AML between March 1982 and January 1994. Of these, 13 had a history skin relapse of 23.1% in this group. Patients with AML and leukemia cutis have a remarkable prop...