PubMed Health⌕ Search

Biomedical subjects

M L Bloom

Publications and source records attributed to M L Bloom.

32 records · Page 2Linked to original sources

Prognostic importance of cytogenetic abnormalities in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia is recognized as having a variable prognosis, but its staging has depended exclusively on anatomical sites of involvement and the presence or absence of anemia and thrombocytopenia. The recent availability of techniques permitting cytogenetic analysis of malignant B lymphocytes led us to examine the karyotypic abnormalities in chronic lymphocytic leukemia and to correlate them with clinical stage, progression of disease, and survival. Of 53 patients with metaphases adequate for study who were followed for a minimum of one year, 21 (40 per cent) had abnormal karyotypes, of which trisomy 12 was the most frequent (25 per cent). Abnormal karyotypes were found to be significant correlates of advanced clinical stage (P less than 0.005) and of shortened survival (P less than 0.05). We conclude that cytogenetic analysis provides useful clinical and prognostic information in patients with chronic lymphocytic leukemia.

Aged↗

Cytogenetic studies in 77 patients with chronic lymphocytic leukemia: correlations with clinical, immunologic, and phenotypic data.

Cytogenetic analyses by G-banding and/or Q-banding techniques of polyclonal B cell mitogen-stimulated peripheral blood lymphocytes in 77 patients with chronic lymphocytic leukemia were carried out in the present study. Adequate metaphases were obtained in 65 patients (84%). Of 29 patients with abnormal karyotypes, ten (34%) had trisomy 12 as the sole abnormality, eight (28%) had trisomy 12 in combination with other karyotypic changes, and the remaining 11 had various karyotypic changes other than trisomy 12. There was a significant relationship between the abnormal karyotype and disease status, clinical stage, lymphocyte count, bone marrow infiltration pattern, monoclonal IgM gammopathy, and urinary monoclonal-free light chain status. Six of seven patients (87%) with trisomy 12 only had stage 0-11 disease, whereas all eight patients with trisomy 12 with other changes had stage III or IV disease (P less than .02). However, of nine patients with other karyotypic changes without trisomy 12, five had stage 0-II and four had stage III or IV disease. These observations suggest that trisomy 12 may be the primary or the earliest karyotypic change in a majority of aneuploid patients with chronic lymphocytic leukemia, and that other karyotypic changes in addition to trisomy 12 may develop as a result of clonal evolution, dedifferentiation, or therapy. Of nine patients in whom autopsy studies were carried out, four were found to have diffuse histiocytic lymphoma or Richter's syndrome (three with trisomy 12 in combination with other chromosome changes and one with normal karyotype). Our findings clearly demonstrate that cytogenetic study may be of value in the clinical and prognostic evaluation of patients with chronic lymphocytic leukemia.

B-Lymphocytes↗

Bone marrow infiltration patterns and their prognostic significance in chronic lymphocytic leukemia: correlations with clinical, immunologic, phenotypic, and cytogenetic data.

Bone marrow biopsies were prospectively performed on 75 patients with chronic lymphocytic leukemia (CLL). There was a highly significant relationship (p less than 0.002) between clinical stages and bone marrow infiltration patterns. Ten (50%) of 20 patients with diffuse patterns died; the estimated median survival time for these patients was 87 months. In contrast, only six (11%) of 55 patients with nondiffuse patterns died; the estimated median survival time for these patients could not be computed. When both clinical stage and infiltration pattern were evaluated for survival, a highly significant association between clinical stage and survival time was still observed (p less than 0.003) whereas bone marrow infiltration pattern was no longer significant. A significant association was also observed between bone marrow infiltration patterns and absolute lymphocyte counts (p less than 0.0005), Fc-receptor-positive cells (p less than 0.002), 3H-thymidine uptake of leukocytes (p less than 0.01), serum alkaline phosphatase levels (p less than 0.05), monoclonal urinary-free light chain status (p less than 0.05), and cytogenetics of leukemic cells (p less than 0.05). These observations lead to the conclusion that in an overall prognostic evaluation of patients with CLL, although bone marrow histopathology may have no additional value over a well-established clinical staging system, as a whole, it may be of clinically predictive value in disease progression of patients with stage I and II.

Adult↗

Lack of T cell antigen expression on hairy cells of B cell origin after in vitro exposure to PHA.

The malignant monoclonal population in hairy cell leukemia (HCL) has been variously ascribed to be of myeloid, B, or even T cell origin. Recent data have been interpreted as suggesting that hairy cells (HC) may concomitantly or serially express both B and T surface determinants, a phenomenon which, if verified, would be unique among the lymphoproliferative malignancies. Data described here, however, demonstrate that (1) at least the majority of HCL are phenotypically of B cell derivation, and (2) the initial B cell phenotype is retained and solely expressed on cultured as well as phytohemagglutinin (PHA) activated monoclonal malignant HC.

Adult↗

Benign monoclonal B cell lymphocytosis--a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients.

From 1951 through 1978, we have seen 20 cases of stage O chronic lymphocytic leukemia (CLL) without disease progression for 6.5-24 years. The cohort included 7 males and 13 females, aged 48-77 years at the time of diagnosis. None presented with anemia, thrombocytopenia, or neutropenia nor developed cytopenias during follow-up. Mean total lymphocyte count in these patients was 20,100/microL, with ranges from 10,000 to 43,700 at the time of diagnosis, and was 20,600, with ranges from 1,000 to 47,200, at last follow-up. Of 12 patients studied, 8 and 4 were phenotyped as heavy chain mu delta- and mu-type, respectively, with 7 kappa- and 4 gamma-type (no light chain was detectable in one patient). Of 13 patients studied, one had a slightly elevated IgG level and two had slightly depressed serum IgA and IgM levels. All patients had positive delayed hypersensitivity responses to at least one of five skin test antigens. Each of seven patients studied for an in vitro leukocyte thymidine uptake had a low level of [3H]thymidine incorporation. Nine of 12 patients studied had elevated total T cells, and the remaining 3 had normal T cell counts. In vitro unseparated lymphocyte response to phytohemagglutinin showed normal kinetics of DNA synthesis, with a peak response on day 3 or 4 of culture in 4 and slightly or moderately depressed and/or delayed kinetics in 8 patients studied. Cytogenetic analyses by Q- or G-banding techniques of polyclonal B cell mitogen-stimulated lymphocytes in all six patients studied showed normal karyotypes. These data are consistent with a previously undescribed syndrome involving a monoclonal B cell lymphocytosis, a prolonged asymptomatic or benign clinical course, and essentially normal humoral and cellular immunity and normal karyotype. Our observations indicate that these 20 patients with stage O CLL have a benign clinical course and that they may also be designated as benign monoclonal B cell lymphocytosis ( BMBL ), a benign variant of CLL.

Aged↗

Use of phenobarbital and high doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in the treatment of brain tumor-bearing mice.

It has been shown that the nitrosoureas are substrates for hepatic microsomal enzymes in vitro and that phenobarbital (PB) administered in multiple doses prior to nitrosourea administration significantly reduces the activity of the nitrosoureas in murine brain tumor models. In the present study, the effect of PB on 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was assessed by determining the CCNU dose which would result in the long-term survival of 50% of the treated mice, and the CCNU dose which would result in the toxic death of 50% of the treated mice, with or without PB pretreatment in C56BL/6J mice. The therapeutic index, the CCNU dose which would result in the long-term survival of 50% of the treated mice, per the CCNU dose which would result in the toxic death of 50% of the treated mice, without PB pretreatment was 2.1; the therapeutic index of CCNU after PB pretreatment was 1.7. There is no significant difference between the therapeutic indices. Thus, the reduction in the tumoricidal activity of CCNU after PB pretreatment was restored by increasing the dose of CCNU without a significant change in its lethal toxicity.l

Animals↗

Possible specific chromosome change in prolymphocytic leukemia.

The chromosomes of unstimulated and stimulated blood lymphocytes from 5 cases with B-cell prolymphocytic leukemia (PLL) were examined following the use of polyclonal B-cell activators (PBA). Banding techniques revealed a common and specific chromosome abnormality to be present in each of the cases, which was due to a translocation between chromosomes 6 and 12 (t(6;12)(q15;p13]. The fact that this specific chromosome change has not been reported in other lymphoproliferative disorders may indicate that PLL is a distinct clinical entity and different from other lymphoproliferative disorders, whether it occurs de novo or complicates chronic lymphocytic leukemia (CLL).

Aged↗

Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status.

In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed.

Adult↗

Observations on going coed in a correctional center.

When a school for delinquent girls converts to a coeducational program it faces major problems, including staff attitudes, residents' reactions, and the control of destructiveness, sexual acting out, and drugs.

Acting Out↗

Heterophile antibodies in pathologic human sera resembling antibodies stimulated by foreign species sera.

Studies were performed on heterphile antibodies originally described by Hanganutziu and Deicher and referred to as H-D antibodies. It was confirmed that these antibodies appear as a result of injections of foreign species sera. They differ from Forssman antibodies by combining with bovine erythrocytes and from Paul-Bunnell antibodies by reacting with guinea-pig kidney. it was demonstrated that H-D antibodies react in double diffusion gel precipitation tests with: (1) crude extract of bovine erythrocyte stromata; (2) purified fraction of this extract devoid of Paul-Bunnell antigen; (3) whole bovine serum and sera of several other species; and (4) thermostable ethanol-insoluble freactions of serum and organs of oxen and several other species. These various antigenic preparations gave usually reactions of complete or partial identity with each other. In several instances, two or even three precipitation lines could be detected. H-D negative human erythrocytes became coated with H-D antigen upon simple incubation with H-D-positive sera. H-D antibodies were also detected in some pathological human sera without any indication that the patients had ever received injections of foreign species sera. Such antibodies were undistinguishable from H-D antibodies engendered by injections of foreign sera.

Adult↗