Biomedical subjects

J M Trujillo

Publications and source records attributed to J M Trujillo.

At least 73 records · Page 4Linked to original sources

PubMed1988

Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome.

An analysis was conducted of clinical and laboratory variables associated with response to remission induction therapy and remission duration in 440 patients with acute myelogenous leukemia treated between 1975 and 1983. The complete remission rate was 259/440 (59%). Specific cytogenetic abnormalities such as t(8;21), t(15;17), and inv16 were found to be favorable for response to therapy and/or remission duration, whereas those with a normal (diploid) karyotype had an intermediate prognosis. All other karyotypic abnormalities were associated with lower response rates and short complete remission durations. The karyotypes were classified as favorable, intermediate, and unfavorable groups for response and remission duration after allowing for all the other observed clinical and laboratory values related to prognosis. The cytogenetic classification was prospectively validated in an independent test group of 130 patients treated between 1983 and 1986 and showed a consistent relationship to response and remission duration. Logistic regression and proportional hazard models developed from the initial 440 patients were prospectively evaluated in the test group of 130 patients. Clear stratifications of patients into good, intermediate, and poor risk groups were obtained in the prospective tests. The karyotype of the leukemia cells is an independent prognostic variable for response and remission duration in acute myelogenous leukemia.

Analysis of Variance↗

PubMed1988

Heterogeneity in acute undifferentiated leukemia.

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.

Acute Disease↗

PubMed1988

Lineage heterogeneity in acute leukemia with the t(4;11) abnormality: implications for acute mixed lineage leukemia.

Acute leukemia associated with the t(4;11)(q21;q23) abnormality demonstrates marked lineage heterogeneity, including cases with features of acute mixed lineage leukemia. We report 7 patients with acute leukemia with the t(4;11) abnormality in which we have defined the range of lineage commitment associated with this disease utilizing a variety of cell characterization techniques. Each case could be classified either as acute lymphoblastic leukemia (ALL) (5 cases) or acute myelogenous leukemia (AML) (2 cases) based on standard light microscopic criteria supplemented by ultrastructural determination of myeloperoxidase. Evidence for acute mixed lineage leukemia was found in one of the AML patients in which coexpression of CD14 and CD19 surface antigens was demonstrated. Overall, the findings further confirm the lineage heterogeneity previously reported in association with t(4;11) acute leukemia. The implications of the findings as to the pathogenesis of t(4;11) acute leukemia are discussed.

Adult↗

PubMed1988

Flow cytochemical patterns of white blood cells in human hematopoietic malignancies: III. Miscellaneous hemopoietic diseases.

Peripheral blood samples from 48 untreated and 20 treated patients with disease entities that directly or indirectly affect hematopoiesis [dys-myelopoietic syndrome (DMS), refractory anemia with excess blasts (RAEB) or in transformation (RAEBIT), lymphoma, myeloma, acquired immunodeficiency syndrome (AIDS), and solid tumors with uninvolved bone marrow] were measured with the Technicon H-6000 automated hematology analyzer; this instrument provides a differential count on 10(4) white blood cells (WBC) effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Cases with DMS and RAEB showed statistically significantly lower WBC counts than normal, whereas cases with lymphoma showed significantly higher values. No disease entity demonstrated changes in mean peroxidase activity (MPA) that were significantly different from normal, although all disease entities, including cases with solid tumors, showed significantly higher (two to severalfold) proportions of cells with high peroxidase (HPX) content, probably as a reflection of a disturbance of normal hemopoiesis with the emergence of younger granulocytic forms. All cases with paraleukemia (DMS, RAEB, and RAEBIT) showed significantly higher values of large unstained cells (LUC), whereas cases with lymphoma showed significantly lower LUC values. There were no statistically significant differences for any parameter (WBC counts, MPA, HPX, or LUC) among the paraleukemia subtypes. However, based on the displayed trends, a case presenting with dyserythropoiesis, relatively low WBC counts, abnormal HPX values, and LUC below 10% should be suspected for RAEB, whereas the presence of greater than 10% LUC and almost normal or even slightly elevated WBC counts should suggest a more accelerated phase of RAEB. Unless complicated by a leukemic phase, cases of lymphoma or myeloma did not display changes in any of the parameters analyzed by the H-6000. Similarly, patients with AIDS had no overt changes other than a trend to lower WBC counts with occasionally higher or lower absolute lymphocyte counts than normal. The peripheral blood of patients with solid tumors displayed a slight increase in HPX, suggesting an indirect effect on hemopoiesis since careful workup failed to demonstrate bone marrow involvement. Our data demonstrates that an H-6000 analysis has a role in the evaluation and follow-up of all these entities particularly to document leukemic transformation of either lymphoma, myeloma, or RAEB.

Flow Cytometry↗

PubMed1988

HL-60 cell line was derived from a patient with FAB-M2 and not FAB-M3.

The leukemia from which the human cell line HL-60 was derived was classified in 1976 as acute progranulocytic leukemia (APL), although it was recognized to show a number of atypical features. In the ensuing 10 years, the concept of APL and its integral association with t(15;17) has evolved, and the concept of APL as a morphologically recognizable entity has become embodied in the term French-American-British classification M3 (FAB-M3). It is now recognized that not every case of leukemia with a high proportion of progranulocytes can be classified as FAB-M3. We reviewed the light and ultrastructural morphology of the original diagnostic material from this case, and we report that the leukemia from which HL-60 was derived does not conform to the currently recognized entity of FAB-M3 and is more appropriately classified as an acute myeloblastic leukemia with maturation, FAB-M2.

Adult↗

PubMed1987

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte--macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 micrograms per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.

Adult↗

PubMed1987

Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification.

By means of the polymerase chain reaction (PCR) technique, DNA sequences were amplified that flank the crossover sites of a characteristic chromosomal translocation for follicular lymphomas, t(14;18)(q32;q21). This technique permitted the detection of cells carrying the t(14;18) hybrid DNA sequences at a dilution of 1:100,000. The remission marrow and blood samples of a patient with follicular lymphoma and the t(14;18) failed to show any abnormality by morphological examination and conventional Southern blot analysis. However, the t(14;18) hybrid DNA sequences were detected by the PCR technique. Thus, this technique is a highly sensitive tool to detect minimal residual cells carrying the t(14;18) and has the potential to identify a subpopulation of patients with subclinical disease.

Base Sequence↗

PubMed1987

Therapeutic modalities for central nervous system involvement by granulocytic sarcoma (chloroma) in children with acute nonlymphocytic leukemia.

Four cases of central nervous system involvement by granulocytic sarcoma (three intracranial and one paraspinal) in children with acute nonlymphocytic leukemia (FAB M1 or M2 subtype) are presented, and therapeutic modalities are discussed. All tumors were noted at initial presentation with diagnosis being made on clinical and radiological findings without biopsy. All patients had karyotypic abnormalities: three had translocation of chromosomes 8 and 21, and one had an unspecified hypodiploid clone. The three patients who developed intracranial tumors responded well to triple agent (cytosine arabinoside, hydrocortisone, and methotrexate) intrathecal chemotherapy and systemic chemotherapy, with or without local irradiation, as evidenced by rapid disappearance of the tumors. Two children are disease-free after 17 and 57 months. One patient with paraspinal tumor failed to achieve a systemic remission but had no evidence of granulocytic sarcoma at autopsy. Thus, the prognosis of CNS granulocytic sarcoma is not uniformly gloomy if treated aggressively by combined modalities. The value of surgical intervention in terms of primary management, however, is limited.

Acute Disease↗

PubMed1987

Untreated prostatic carcinoma is not associated with frequent thrombohemorrhagic disorders.

We conducted an evaluation of the hemostatic integrity of patients with untreated cancer of the prostate. Of 60 patients analyzed retrospectively, only 1 had a mild case of disseminated intravascular coagulation, possibly associated with concomitant estrogen therapy, and in 1 patient mild deep vein thrombosis developed preoperatively, also possibly associated with multiple medications for concurrent disorders. Of 16 other patients prospectively evaluated on admission, only 1 had frankly abnormal levels of fibrinopeptide A unaccompanied by other coagulation abnormalities. Occasional individuals had minimal, negligible deviations of partial thromboplastin times, thrombin time, or antithrombin III values. In none of these patients did hemostatic complications develop during their hospital stay. These results demonstrate that although an occasional coagulation abnormality may occur in patients with cancer of the prostate (albeit with a lower incidence than in other neoplasms), this malignancy does not require increased precautions with respect to those given to the patient population at large.

Adult↗

PubMed1987

DNA aneuploidy in adult acute leukemia.

Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.

Adult↗

PubMed1987

The technicon H*1--an automated hematology analyzer for today and tomorrow. Complete blood count parameters.

The performance of the Technicon H*1 was evaluated in the computerized, high-volume hematology laboratory at M.D. Anderson Hospital and Tumor Institute and compared with that of reference instrumentation used for routine patient care. The precision, linearity, and lack of carry-over of this instrument was excellent for the entire dynamic range of all nine tested parameters (white blood cells [WBCs], red blood cells [RBCs], hemoglobin [Hgb], hematocrit [Hct], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], red blood cell distribution width [RDW], and platelets [Plts]). Coefficients of correlation for all directly measured parameters were always 0.98 or greater, with the exception of the MCV and RDW parameters, for which r = 0.89 and 0.93, respectively. Special emphasis was placed on WBC and Plt counts at low ranges. When compared with reference methods the correlation for both parameters was very good, r = 0.99 for WBCs less than 4.0 X 10(3)/microL (4.0 X 10(9)/L) and 0.91 for Plt less than 100 X 10(3)/microL (100 X 10(9)/L). These excellent performance characteristics for the CBC parameters, combined with the ability of the analyzer to perform a full WBC differential (to be described in the next report), make the H*1 a superior advancement in the field of automated hematology.

Autoanalysis↗

PubMed1987

Molecular analysis of chromosome 22 breakpoints in adult Philadelphia-positive acute lymphoblastic leukaemia.

The Philadelphia (Ph) translocation, t(9:22)(q 34:q11), is found in the majority of patients with chronic myelogenous leukaemia (CML) as well as in approximately 20% of adult acute lymphoblastic leukaemia (ALL) patients. The chromosome 22 breakpoint in CML has been localized within a restricted 5.8 kb segment of DNA known as the breakpoint cluster region (bcr). To investigate the chromosome 22 breakpoint in ALL, we analysed five adult Ph-positive ALL patients for bcr rearrangement. Rearrangement was detected within bcr in two patients. However, in one patient the break occurred 5' to the first exon of bcr and in two patients the bcr region was not involved. We conclude that the identical cytogenetic marker, t(9:22), may yield a different genomic configuration in ALL and CML.

Acute Disease↗

PubMed1987

Flow cytochemical patterns of white blood cells in human haematopoietic malignancies. II. Chronic leukaemias.

Peripheral blood samples from 73 patients with chronic leukaemia were measured with the Technicon H-6000 automated haematology analyser to provide flow cytochemical (peroxidase content) and volume (light scatter) discriminated scattergram patterns. For chronic granulocytic leukaemia (CGL), these patterns were so reproducible and distinct that they allowed an immediate diagnosis even without the benefit of microscopic examination. Relative and absolute basophilia was an invariable feature, and remained detected by the H-6000 even when the patient was in haematologic and cytogenetic remission or progressed into blast crisis (BC). Most patients in BC also demonstrated an inordinately high number of large unstained cells (LUC) and high proportions of 'lymphocytes' (small blasts with no peroxidase content by visual inspection). Thus, for patients with CGL, LUC values above 10%, and/or steady increments in the proportion of 'lymphocytes', merit concern as these changes may herald an accelerated phase of disease. The scattergram pattern of untreated chronic lymphocytic leukaemia (CLL) showed a dense accumulation of data points within the lymphocytic 'box' with a small cluster of granulocytic elements. Most patients also had a frankly abnormal proportion of LUC. Sixteen patients with CLL were compared for ratios of LUC to lymphocytes and stage of disease; patients with the most advanced stage (IV) had the highest, statistically significant values, than the patients with more benign disease. Thus, it is possible that follow up with this instrument of patients with CLL will also allow early detection of an impending prolymphocytoid transformation (accelerated phase) of this disease.

Cell Separation↗

PubMed1987

Flow cytochemical patterns of white blood cells in human haematopoietic malignancies. I. Acute leukaemias.

Peripheral blood samples from 118 patients with acute leukaemia (68 untreated; 50 treated) were measured with the Technicon H-6000 automated haematology analyser. This instrument provides, in addition to measurements of the classical haematology parameters (i.e. cell counts, haemoglobin concentration, etc.), a differential count on 10(4) WBC effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Disregarding RBC and platelet counts and their volume distribution profiles, the most important diagnostic parameters for leukaemic disease were the WBC count, the WBC differential count, and the proportions of large unstained cells (LUC) and high peroxidase (HPX) cells obtained by the automated differential count as well as the mean value of the WBC peroxidase content distribution (MPA). Granulocytic leukaemias had lower MPA than normal and lymphocytic leukaemias had MPA values above normal. M1 leukaemias were also characterized by large proportions of LUC and low fractions of HPX, while M2 leukaemias showed low LUC with high HPX. M3 leukaemias had low LUC and very high HPX. M4 leukaemias had large LUC and 'monocytic' components and a modest fraction of HPX. M5 leukaemias had very large numbers of LUC, 'monocytes' and 'lymphocytes' and a normal HPX. For M1 leukaemia, the presence of less than 7% LUC following induction treatment was related to morphological changes of normal cells induced by chemotherapy while LUC above 10% usually indicated unsuccessful induction associated with the presence of residual blasts. If treatment was successful, M2 and M3 leukaemias characteristically decreased their HPX population. All M4 leukaemias studied by us failed to enter remission and continued to display high proportions of HPX and LUC. Similarly, most M5 leukaemias had a poor response to treatment and always showed a very high proportion of LUC. Untreated lymphocytic leukaemias demonstrated high LUC, normal HPX and a high proportion of 'lymphocytes'. Hairy cell leukaemias showed almost equal proportions of 'lymphocytes' and LUC. Successful chemotherapy of all lymphoid leukaemia entities was associated with rapid decreases in LUC, slower decrements of 'lymphocytes' and moderate and transient increments in HPX. Thus, flow cytochemistry can assist not only in the segregation of acute leukaemias along with FAB classification with nonmorphologic criteria, but also in the follow up of patients with these diseases.

Acute Disease↗

PubMed1987

The localization of the human myeloperoxidase gene is in close proximity to the translocation breakpoint in acute promyelocytic leukemia.

The human myeloperoxidase (MPO) gene has recently been cloned in our laboratory. Southern blot hybridization of our MPO cDNA to DNA from a somatic cell hybrid clone panel revealed that the MPO cosegregated with human chromosome 17. In situ hybridization mapped the MPO gene to chromosome 17q22-24. Although this location is close to the translocation breakpoint which occurs in acute promyelocytic leukemia (APL), t(15;17)(q22;q21-22), Southern blot hybridization with different restriction-digested genomic DNA samples from four APL patients did not reveal MPO gene rearrangement. However, RNA dot-blot hybridization showed that APL patients with the translocation expressed high levels of MPO mRNA. This observation raises the possibility that the high levels of MPO gene expression in APL could be due to the arrest of leukemic cells at a specific stage of differentiation or a consequence of the translocation.

Chromosome Mapping↗

PubMed1987

T-cell receptor gamma chain gene rearrangement in acute myelogenous leukemia--evidence for lymphoid lineage prematurity.

The T-cell receptor gamma chain (TcR gamma) gene is rearranged in early T-cell differentiation. However, rearrangement of the TcR gamma gene is not specific for T lineage since it has also been noted in B-cell neoplasia. TcR beta gene rearrangement and heavy chain immunoglobulin gene rearrangement have also been reported in acute myelogenous leukemia (AML). Because of the previous reports of lineage heterogeneity at the molecular level, we analyzed seven patients who met the standard criteria for AML by Southern blot hybridization with a TcR gamma gene probe, a TcR beta gene probe, and an immunoglobulin heavy chain JH gene probe. In two samples, the TcR gamma gene was rearranged. One of these two samples also had rearrangement of the immunoglobulin JH gene. None of the seven samples showed TcR beta gene rearrangement. The two samples with TcR gamma gene rearrangement also showed 25% and 80% of terminal deoxynucleotidyl transferase (TdT) positivity, respectively. Both samples expressed myeloid lineage-associated antigens without any lymphoid lineage-associated antigens. Our studies indicate that TcR gamma gene rearrangement is not specific for lymphoid lineage and the presence of TcR gamma and immunoglobulin JH gene rearrangements without expression of lymphoid lineage-associated markers supports the concept that there is lymphoid lineage prematurity in AML.

Gene Rearrangement, gamma-Chain T-Cell Antigen Rec↗

PubMed1987

Underestimation of monoclonal proteins by serum protein electrophoresis on cellulose acetate.

Our study of 95 serum samples from 37 patients with monoclonal gammopathy revealed distorted irregular monoclonal (M) protein bands after serum protein electrophoresis (SPE) on cellulose acetate membrane. In 71 (75%) of the 95 sera, the M-protein was underestimated and the albumin concentration overestimated. Dilution of the serum sample before SPE eliminated the abnormality of the M-protein bands. By SPE, the mean albumin concentration in these 71 undiluted sera was 45.8 (SD 7.4) g/L vs 37.9 (SD 5.8) g/L for the diluted sera; moreover, this was true of individual samples: measured albumin concentration in each diluted serum sample was always less than in the undiluted serum. As measured by the bromcresol green dye-binding method, the albumin concentration was 32.8 (SD 5.9) g/L. Similarly, the M-protein concentration in SPE was 49.5 (SD 12.3) g/L for the undiluted sera vs 61.8 (SD 15.1) g/L for the diluted sera, and the M-protein concentration in each diluted serum sample always exceeded that in the undiluted serum. Underestimation of M-protein limits the usefulness of M-protein measurement in evaluating the patient's response to therapy and for early detection of disease progression. SPE strips should be carefully inspected visually, and sera with M-protein band abnormalities should be diluted and re-assayed if SPE is to quantify concentrations of M-protein and albumin accurately.

Blood Protein Electrophoresis↗

PubMed1987

Therapy of chronic myelogenous leukemia with recombinant interferon-gamma.

Recently, we reported that recombinant interferon-alpha (rIFN-alpha) can induce hematologic remissions and cytogenetic improvement in newly diagnosed Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) patients. Although IFN-gamma is a structurally distinct molecule, this agent suppresses in vitro hematopoietic progenitor cells in a fashion similar to that of IFN-alpha. Therefore, we initiated a study of rIFN-gamma at doses of 0.25 to 0.5 mg/m2/d intramuscularly in patients with Ph-positive benign-phase CML. Twenty-six of 30 patients entered in the study were evaluable. Six patients have achieved a complete hematologic response; four, a partial hematologic response. The median follow-up period of patients who are in complete remission is 7.5 months (range, 5 to 12 months). No relapses have occurred among the complete responders. So far, five patients have had cytogenetic improvement with emergence of 5% to 45% diploid cells in the bone marrow. Fever and flulike symptoms were the most common side effects, with partial tolerance often developing after about 1 week. The majority of patients tolerated therapy with minimal change in performance status. In conclusion, rIFN-gamma has demonstrated clinical activity in CML. On the basis of these observations and the in vitro synergistic growth-inhibitory effects of IFN-alpha and IFN-gamma, we have started trials of combination IFN therapy in CML patients.

Adult↗