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Biomedical subjects

O M Garson

Publications and source records attributed to O M Garson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia.

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.

Adult↗
PubMed1985

Chronic granulocytic leukemia: correlation of blastic transformation type with karyotypic evolution.

Over a 3-year period, 26 patients with Philadelphia chromosome-positive chronic granulocytic leukemia were studied cytogenetically in both the chronic and blastic transformation phases of the disease; a further three patients were studied only after blastic transformation. Sixteen were considered to have adequate evidence of the type of transformation and form the basis of the report, where chromosome changes have been correlated with the morphological type of blastic transformation. Seven patients developed a myeloblastic transformation, seven a lymphoblastic transformation, and two an erythroblastic transformation. All patients in the myeloid group acquired one or more of the nonrandom changes associated with CGL blastic transformation, viz. +8,i(17q), +19, +22q-. Patients in the lymphoblastic group acquired structural abnormalities, apparently random in nature and usually in a small percentage of cells. The two patients with erythroblastic transformation developed markedly hyperdiploid cells (greater than 50 chromosomes) with both numerical and structural abnormalities. Patients in the lymphoblastic group appeared to have a slightly better prognosis than the myeloid group, whilst the patients with erythroblastic transformation had a very poor prognosis.

Adult↗
PubMed1985

t(1;3)(p36;q21) in acute nonlymphocytic leukemia: a new cytogenetic-clinicopathologic association.

A number of specific chromosomal abnormalities have been associated with distinctive clinical and/or morphological subtypes of acute nonlymphocytic leukemia (ANLL) in recent years. We have studied three patients with ANLL and t(1;3)(p36;q21). Each had weakness as their major complaint, a moderately severe anemia and, for ANLL, a relatively high platelet count. All three demonstrated abnormalities of the megakaryocytic, erythroid and granulocytic lineages. Most striking was the dysmegakaryocytopoiesis. The blasts in all three patients showed relatively few azurophilic granules, one to four prominent nucleoli, and rare peroxidase positivity. No patient had Auer rods. No patient responded to standard chemotherapy regimens. The data suggest that t(1;3)(p36;q21) identifies a new cytogenetic-clinicopathologic subtype of ANLL.

Acute Disease↗
PubMed1984

Translocation 1;19--a new cytogenetic abnormality in acute lymphocytic leukemia.

A study of the chromosomes of 125 consecutive patients with acute lymphocytic leukemia (ALL) showed the same translocation between chromosomes #1 and #19 in 5 patients. In 4 of the 5, the t(1;19)(q21;q13) was present at diagnosis. The fifth patient, who had Philadelphia chromosome positive (Ph1+) ALL, developed t(1;19) in first relapse. Trisomy 1q was involved in 2 of the 5 patients; 3 patients had additional abnormalities. All patients had low white cell counts at presentation (less than 35 X 10(9)/L), and the 4 patients tested had common ALL antigen (CALLA) positive leukemic blast cells. All achieved complete remission, including the Ph1+ ALL patient in first relapse, and survival times ranged from 4 to 21+ mo from the time the t(1;19) first appeared. Our data suggest that t(1;19) is a previously unrecognized nonrandom structural abnormality in ALL that is also found in other lymphoid malignancies. Unlike the other specific translocations, it is not associated with a poor prognosis.

Adolescent↗
PubMed1984

A complicated but nonrandom karyotype in preleukemia.

A patient with preleukemia who possessed a complicated hypodiploid karyotype in 100% of bone marrow cells is described. The clinical, hematologic, and cytogenetic features showed a marked similarity to a patient with preleukemia described by Watt et al. [1]. Both patients terminated their disease in acute nonlymphocytic leukemia. Another patient with similar cytogenetic features, but who presented in the acute leukemic phase of polycythemia rubra vera, also is described. All three patients possessed a translocation involving chromosome #11 at band p15. This, together with many numerical and structural abnormalities, particularly those involving chromosomes #5, #7, and #17, may prove useful in defining a variety of preleukemia with a poor prognosis.

Aged↗
PubMed1984

Silver bands in chronic granulocytic leukemia: I. Increased banding associated with blastic transformation.

We have tested the proposal that the level of silver banding in leukemic cells of Ph1 + chronic granulocytic leukemia (CGL) patients increases as the disease progresses. Blood and/or bone marrow cells from 14 patients were cultured for 24 hr before banding. In all but one case, there were two populations of mitoses, those with silver bands on their nucleolar organizing regions (NORs) and those without. The percentage of cells that banded was higher, on average, in cultures from 7 patients in blastic transformation (80%) than in 8 chronic cases (36%) or in one accelerated phase (49%). Also, the mean number of NORs stained in banded cells was higher in blastic phase (6.9) compared with chronic phase cells (4.4). Hyperdiploid cell lines were present in four cases of myeloblastic transformation. All such cells were silver banded, and the mean fraction of NORs banded in them was relatively high. An increase in silver banding with time was shown in two of the patients. It seems that silver banding does increase in CGL cells as the disease progresses. This may arise either through an increase in the rate of ribosomal RNA synthesis in leukemic cells present in the blastic phase or possibly by a decrease in the rate of degradation (or processing) of newly synthesized rRNA.

Adult↗
PubMed1984

Clinicopathological characteristics of acute lymphoblastic leukemia with the 4;11 chromosome translocation.

Analysis of the bone marrow karyotype in 109 consecutive untreated patients with acute lymphoblastic leukemia (ALL) by the G-banding technique revealed the presence of a translocation between specific sites on the long arms of chromosomes 4 and 11, [t(4;11) (q21;q23)] in 3 adults and 2 children. Splenomegaly was present in all patients, marked leukocytosis in 4, and retinal hemorrhages in the absence of significant mucocutaneous bleeding in 3. Complete remission defined by conventional morphological criteria was achieved with combination chemotherapy in all instances, but the duration of remission was brief in 3. Three patients were studied in relapse, and clonal evolution was found to have occurred in 2. Analysis of our data in conjunction with other published reports suggests this specific karyotypic abnormality characterizes a small subgroup of ALL in which there is a strong association with recognized clinical and laboratory indices of poor prognosis, in particular its frequent occurrence in children under the age of 2.5 yr. There is a propensity to undergo clonal evolution, and the possibility exists that such a development is associated with poor prognosis.

Adolescent↗
PubMed1984

Chromosome abnormalities in leukaemia and lymphoma.

Using improved techniques, chromosome abnormalities have now been identified in the majority of haematological disorders. Structural abnormalities have proved specific for morphological varieties of both leukaemia and lymphoma, in some cases specific for cell type, as in acute promyelocytic leukaemia, in others specific for cytogenetic varieties within a morphological group, as in the t(8;21) variety of acute myeloid leukaemia (M2). The 9;22 translocation found in most cases of chronic granulocytic leukaemia has been well recognised as a diagnostic feature for many years, and evolution of this disease to its acute leukaemic phase is accompanied by additional abnormalities. Chromosome changes in acute lymphocytic leukaemia are considered to be the most important independent prognostic indicator in this disease and more recently, changes which may have therapeutic implications have been found in almost all patients with Non Hodgkin's Lymphoma. Chromosome studies should be performed on the involved cells in all patients presenting with leukaemia and lymphoma for diagnosis and prognosis, and to establish a base line for remission and evolution of the disease. Such studies are also yielding valuable information regarding the derivation and aetiology of these disorders.

Burkitt Lymphoma↗
PubMed1983

Fluorodeoxyuridine synchronization of bone marrow cultures.

A method for synchronization of bone marrow cells with fluorodeoxyuridine (FdU) is presented and compared with methotrexate (MTX) synchronization. FdU has the advantage of not requiring cell washing for release of the DNA synthesis block and was found to be more beneficial for bone marrow cultures because it generally produced a higher mitotic yield and was less damaging to chromosomes. Late-replication banding, produced after releasing the FdU block with bromodeoxyuridine (BrdU), indicated that cells in midsynthesis at the time of the block release were those that showed the most increase in chromosome length and the most improvement in the quality of the metaphase spread. Therefore, because bone marrow cells have a longer cell cycle time than stimulated lymphocytes, a minimum of 7-8 hr culture after release of the block is recommended to give optimal results. It was also found that, to increase the yield of mitoses, at least 6-8 hr of growth was necessary before the addition of either of these synchronizing agents.

Bone Marrow↗
PubMed1983

The influence of colcemid concentration on mitotic index and length of bone marrow chromosomes.

Bone marrow cells from 25 patients with different hematological disorders were cultured overnight and then exposed to colcemid, varying both concentration and time of exposure, in order to obtain optimal results. PHA stimulated lymphocytes were treated in a similar manner for comparison. Results showed that with concentrations at or below 0.4 microgram/ml, the mitotic index of PHA stimulated lymphocytes was reduced and the metaphase spreads were of poor quality, but spreads of bone marrow chromosomes were not adversely affected at even much lower concentrations. Furthermore, both chromosome length and mitotic index were found to increase with lower concentrations. These observations, together with results obtained by comparing mitotic indices after varying exposure times, suggest that bone marrow cells may be inhibited from passing through G2 by high concentrations of colcemid. Thus by lowering the concentration of the colcemid for bone marrow cultures, we have been able to increase greatly the yield of bandable metaphases.

Bone Marrow↗
PubMed1982

Double 9;22 translocation with hyperdiploidy appearing in blastic transformation of chronic granulocytic leukemia.

Chromosome studies in a 26-year-old female with Ph1-positive chronic granulocytic leukemia showed the development of both hyperdiploid and tetraploid cell lines in the blastic transformation phase. An additional 9;22 translocation and additional chromosomes No. 8, 11, 13 and 22 were found in the hyperdiploid cell line. This unusual finding suggests that the hyperdiploidy may have developed from misdivisions in the tetraploid cell line rather than by the more accepted mechanism of nondisjunction or selective endoreduplication from a diploid cell.

Adult↗