Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (>50 chromosomes) are considered to have a relatively good prognosis. The specific extra chromosomes are not random; extra copies of some chromosomes occur more frequently than those of others. We examined the extra chromosomes present in high hyperdiploid ALL to determine if there were a relation of the specific extra chromosomes and modal number (MN) and if the extra chromosomes present could differentiate high hyperdiploid from near-triploid and near-tetraploid cases. Karyotypes of 2,339 children with ALL and high hyperdiploidy at diagnosis showed a distinct nonrandom sequential pattern of gain for each chromosome as MN increased, with four groups of gain: chromosomes 21, X, 14, 6, 18, 4, 17, and 10 at MN 51-54; chromosomes 8, 5, 11, and 12 at MN 57-60; chromosomes 2, 3, 9,16, and 22 at MN 63-67; chromosomes 1, 7 13, 15, 19, and 20 at MN 68-79, and Y only at MN >or=80. Chromosomes gained at lower MN were retained as the MN increased. High hyperdiploid pediatric ALL results from a single abnormal mitotic division. Our results suggest that the abnormal mitosis involves specific chromosomes dependent on the number of chromosomes aberrantly distributed, raising provocative questions regarding the mitotic mechanism. The patterns of frequencies of tetrasomy of specific chromosomes differs from that of trisomies with the exception of chromosome 21, which is tetrasomic in a high frequency of cases at all MN. These results are consistent with different origins of high hyperdiploidy, near-trisomy, and near-tetrasomy.

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus- leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.

Representatives of three subgenera of Hylobatidae, Hylobates (Symphalangus) syndactylus, H. (Nomascus) concolor and H. (Hylobates) agilis were compared karyotypically by G-banding, and silver staining. A greater degree of similarity (30-55%) was found among these groups than previous reports suggest; however, these figures are still considerably lower than chromosome similarities characteristic of all other catarrhine groups. Inversion, translocation, fission, and fusion have all played a role in restructuring hylobatid chromosomes since a common hominoid ancestor. H. syndactylus and H. concolor show the greatest G-band correspondence, and in addition share an unusual C-band distribution and an extremely rare nucleolar organizing region placement (on the Y chromosome). The latter two are probably shared derived traits, suggesting that these two species shared a common ancestor not shared by other hylobatids. These data suggest a branching order for these three hylobatid groups different from those derived by other morphological and biochemical methods.