Search

Second malignancies occur with a greater frequency in patients with chronic lymphatic leukemia than in the general population. Previously, 20 patients having CLL have been reported as developing acute leukemia, but no cases of development of chronic granulocytic leukemia have been observed. In the present report, we will describe patients with Ph1 chromosome positive CGL associated with previously described CLL. One patient received total body radiation treatment for his CLL, while the second was not treated. It is apparent that previous therapy may not necessarily be a prerequisite for the development of a second malignancy in CLL. Cytogenetics offers a useful tool to confirm morphologic criteria in establishing the diagnosis of a second neoplasm.

The nature of the cells which proliferate in response to allogeneic histoincompatible lymphocytes in human mixed leukocyte cultures (MLC) was investigated. Direct information on the differentiation of proliferating cells was obtained in an in vitro chimeric system with T- and B-cell sex chromosome markers. Highly purified T and B cells were prepared from the peripheral blood of three pairs of HL-A genotype identical, MLC-negative siblings of opposite sex by E-rosette sedimentation techniques. Recombined T and B cells of the siblings were stimulated with allogeneic cells, and karyotype analysis of proliferating cells performed. 96% of the proliferating cells were found to carry the sex chromosome marker of the respective T-cell population. These results indicate that proliferation in human MLCs is a feature of T cells.

Thirty patients in the blastic phase of chronic granulocytic leukemia were treated with a combination of vincristine, 2.0 mg/sq m weekly, and prednisone, 60 mg/sq m orally each day. Remission was achieved in nine patients (30%), six of whom had a complete remission, and three had a good partial remission. The survival of responding patients was significantly improved over the nonresponders. Cytogenetic studies were performed on all patients in the chronic phase of the disease, and in 28 during the blastic phase. All were Philadelphia chromosome-positive throughout their course. Aneuploidy developed in 68% of the patients entering the blastic phase. Complete hematologic remission was accompanied by disappearance of aneuploid blast cell lines in the five patients in which they were detected, with return of the chromosomal constitution to that which characterized the chronic phase of their disease. Hypodiploidy in blastic transformation of CGL appeared to predict for a favorable response to vincristine and prednisone. Subsequent relapse of the disease in previously remitted patients was associated with further degrees of aneuploidy, suggesting clonal evolution of a resistant cell line.

An 8-year-old boy with acute lymphocytic leukemia, no longer responsive to conventional chemotherapy after 2 years, was successfully grafted with bone marrow from his HL-A genotypically identical 10-year-old sister. Prior to transplantation, he had received 141 blood component transfusions and had become sensitized to histocompatibility antigens (HL-A), as demonstrated by the presence of circulating lymphocytotoxic antibodies. Except for the occurrence of a possible mild graft-versus-host-reaction and a documented cytomegalovirus infection, the patient remained clinically well until full return of his leukemia 91 days after the transplant. This case demonstrates that bone marrow transplantation can be accomplished between HL-A identical siblings even though the recipient may have been previously sensitized to other HL-A antigens by earlier transfusion. Allogenic bone marrow transplantation offers the opportunity for remissions in patients with leukemia unresponsive to conventional drug therapy.

HIGH incidence of nonspecific abnormal chromosomes in human malignant tumors was noticed in the past ten years.1 To date the finding of the minute chromosome (Ph1) in the bone marrow of patients with chronic myelogenous leukemia represents the only instance of a specific chromosome abnormality unique to a human neoplastic disease.2-5 A recent case of metastatic neuroblastoma with unusual chromosome abnormalities in the direct bone marrow preparation prompted us to review our experience with two additional cases in the hope that some common abnormality would be found. MATERIALS AND METHODS The following three patients with disseminated neuroblastoma were treated at the Clinical Center, National Cancer Institute, National Institutes of Health. Chromosomes of the mitotic cells in bone marrow were studied without prior in vitro culture and in air dried preparations.6 Peripheral blood was cultured for 72 hours and preparations made according to the technique of Moorhead

Cytogenetic studies of marrow cell lines were done in 10 cases of erythroleukemia and in 6 cases of potentially preleukemic refractory megaloblastic anemia. Abnormalities consisting of aneuploidy, increased polyploidy and chromosome breakage were found in 9 cases, 6 in the erythroleukemia group and 3 in the refractory anemia group. Observations in these cases support the concept that erythroleukemia is a clinical variant of acute granulocytic leukemia. They also indicate that marrow chromosome analysis can assist in the diagnosis of cases where leukemia is suspected but not clinically proven.

Serial cytogenetic studies were performed on 179 chronic myelocytic leukemia patients (CML) at the Clinical Center of the National Institutes of Health. Patients were divided into 6 groups according to cytogenetic findings: Ph1 negative (18 patients), Ph1 negative with other chromosomal abnormalities (3 patients), Ph1 positive (116 patients), Ph1 positive and negative (10 patients), Ph1 positive with other chromosomal abnormalities (24 patients), and Ph1 positive which turned to other chromosomal abnormalities (8 patients). Patients who were Ph1 negative and negative with other chromosomal abnormalities (11.8 per cent of total) had the shortest median survival, 12 to 15 months. In contrast, the median survival of patients in the Ph1 positive groups was 31 to 40 months. The development of other chromosomal abnormalities in Ph1 positive patients presaged the terminal stage of the disease.