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Biomedical subjects

J Trujillo

Publications and source records attributed to J Trujillo.

At least 55 records · Page 3Linked to original sources
PubMed1988

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.

Chromosome Aberrations↗
PubMed1988

Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy.

We have detected rearrangement in the breakpoint cluster region (bcr) on chromosome 22 in cells derived from seven chronic myelogenous leukemia (CML) patients who had no cytogenetic evidence of a chromosome abnormality. These Philadelphia (Ph)-negative, bcr rearrangement-positive CML patients had clinical features and laboratory parameters that bore a strong resemblance to those of Ph-positive CML; all patients have shown a favorable response to hydroxyurea, busulphan, or alpha interferon (IFN-alpha) therapy. In one patient, because of the deletion of distal 3' sequences, detection of bcr rearrangement required a large probe that recognized proximal 5' sequences. Cells obtained from five patients were studied by Northern blotting and showed an aberrant 8 kilobase (kb) mRNA indistinguishable from the bcr-abl transcript that is felt to be a pathogenetic factor in Ph-positive CML. In three patients with a normal karyotype, bcr rearrangement was detected at the time of hematologic remission, and represented the only evidence for persistent malignancy. Our results suggest that: (1) the presence of bcr rearrangement in CML is associated with clinical features of Ph-positive disease, even in the absence of the Ph chromosome; (2) deletions occur within bcr and necessitate the use of probes covering both 5' and 3' DNA segments for accurate diagnosis; (3) molecular analysis may provide a useful approach to the follow-up of leukemia therapy in some patients; and (4) these patients respond to hydroxyurea, busulphan, and IFN-alpha therapy.

Adolescent↗
PubMed1988

Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3' bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.

Blast Crisis↗
PubMed1988

Phenotypic and molecular heterogeneity in Philadelphia chromosome-positive acute leukemia.

Philadelphia chromosome-positive (Ph1) acute leukemia is a heterogeneous subset of acute leukemia with a poor prognosis. We studied five patients to determine the potential for phenotypic and molecular heterogeneity. Cellular characterization studies included light myeloperoxidase (L-MPO), terminal deoxynucleotidyl transferase (TdT), ultrastructural MPO (U-MPO), and immunophenotyping by flow cytometry using T11, T3, T4, T8, Leu 1, B1, Leu 12, HLA-DR (la), CALLA (J5), OKM1, My4, My7, My8, My9, and My10. DNA was analyzed for rearrangements of the breakpoint cluster region (bcr), immunoglobulin heavy chain, joining region (JH), immunoglobulin kappa light chain constant region (C kappa), and T cell receptor (TcR beta). RNA dot blots were hybridized by using molecular probes for MPO and TdT. We found that four of five cases were acute mixed-lineage leukemia (AMLL). One patient had acute unclassifiable leukemia. Of the four patients classified as having AMLL, three showed myeloid and lymphoid features, with one patient showing myeloid, T cell, and B cell features. The last case showed T cell and B cell features only. In one patient MPO/RNA was positive in spite of insufficient L-MPO or U-MPO to diagnose acute myelogenous leukemia (AML), thereby suggesting significant MPO gene expression before the production of sufficient MPO protein to meet the French-American-British criteria for AML. Three of the five patients showed rearrangement of bcr (cases 1, 2, and 5). Studies of these five patients support the concepts of molecular and phenotypic heterogeneity in Ph1 acute leukemia, demonstrate a high incidence of AMLL in this subset of acute leukemia, and support the use of lineage-associated molecular probes to define lineage at an earlier stage than previously possible.

Acute Disease↗
PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗
PubMed1987

Therapy of chronic myelogenous leukemia.

While the demonstrated antiviral, antiproliferative, and immunomodulatory properties of interferons have led to a number of theories regarding their potential use in treating individuals with chronic myelogenous leukemia (CML), their limited availability has prevented thorough clinical investigation. However, in 1980, successful cloning of the mature human alpha-A interferon led to the production of large quantities of bacterially synthesized human alpha-A interferon, now designated interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ). This abundance of alfa-2a made possible clinical studies of alpha interferon's capacity to suppress CML Philadelphia (Ph1) clones as well as restore the cells with normal karyotype. The data resulting from these clinical trials indicate that interferon alfa-2a is effective in inducing hematologic remissions in the majority of minimally treated, benign-phase CML, Ph1-positive patients. In some of the patients, treatment resulted in Ph1 chromosome suppression in the bone marrow and in the emergence of cells with a normal karyotype.

Antineoplastic Agents↗
PubMed1987

Toward a clinically relevant cytogenetic classification of acute myelogenous leukemia.

Cytogenetic studies with Giemsa banding were performed on the bone marrow cells of 384 patients with acute myelogenous leukemia treated between 1975 and 1983. An abnormal karyotype was detected in 54% of patients, being present in 100% of metaphases (AA) in 31% and only a proportion of cells (AN) in 22%. Specific translocations or other abnormalities were noted in 22% of patients, the most common of which were t(8;21) (q22;q22) in 7%, t(15;17) (q22;q21) and inv (16) (p13q22) in 5.5%, t(9;22) (q34;q11) in 3% and abnormalities of 11q23 in 1.3%. Loss of the Y chromosome was noted in 21 patients, associated with t(8;21) in 11 patients and the sole abnormality in eight patients (45, X, -Y). Most (66%) of the other abnormalities involved addition of chromosome 8 or loss or deletion of 5 or 7 (+8, -5 or -7, 5q- or 7q- group). The remaining patients had miscellaneous abnormalities (MA). A marked assymetry was noted in the distribution of important clinical prognostic variables such as age, sex, history of an antecedent hematologic disorder and presence of Auer rods within the various cytogenetic categories. The specific translocation/abnormalities were more common in younger patients (p less than 0.01). Analysis of response, remission duration and survival demonstrated that inv 16 and t(8;21) were favorable prognostic categories; diploid, t(15;17) and 45,X,-Y had intermediate prognosis, and all other categories were unfavorable prognostic groups. The response rate and survival for diploid patients (NN) was superior to patients with abnormalities. No difference in response rate, CR duration or survival was noted between the AA and AN groups. A prognostic classification according to cytogenetic category based on clinical associations is proposed which will be tested prospectively in subsequent studies.

Adult↗
PubMed1987

Molecular characteristics of chronic myelogenous leukemia in blast crisis.

We have studied the expression of c-abl and c-myc in leukemic cells of patients in all clinical phases of chronic myelogenous leukemia. We demonstrate that an aberrant 8-Kb c-abl related transcript is present in the RNA of the leukemic cell from all patients with Ph+ CML and that the loss of both normal chromosome #9 is associated with the loss of the normal c-abl related transcripts. This represents direct evidence that the normal c-abl related transcripts derive from the normal c-abl gene locus on the normal chromosome #9, while the aberrant c-abl related transcript in Ph+ CML derives from the hybrid bcr-abl gene formed as a result of the t(9;22). We further demonstrate that trisomy 8 in some instances is associated with enhanced expression of the c-myc oncogene.

Blast Crisis↗
PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗
PubMed1987

Brightness acuity test and outdoor visual acuity in cataract patients.

The disparity between functional outdoor vision and the acuity measured in the standard refracting lane is well known among clinicians. A simple device, the brightness acuity tester (B.A.T.), was developed to predict a patient's functional outdoor acuity. The B.A.T. has an illuminated hemispheric bowl, 60 mm in diameter, with a 12-mm aperture. Fourteen normals and 50 patients with cataracts were tested using the B.A.T. and then tested outside in bright sunlight. The B.A.T. correlated extremely well (r = +0.84, P less than .0001) with the acuities measured outside. There was no decrease in visual acuity in the 14 normal patients, but there was a one to ten line decrease in vision among the cataract patients. Upon retesting, the B.A.T. scores did not vary, while outside testing scores did change due to variable outdoor ambient light levels on sunny days. The B.A.T. is a simple, repeatable, useful test for predicting functional outdoor acuity.

Cataract↗
PubMed1987

Central nervous system complications of a newly recognized subtype of leukemia: AMML with a pericentric inversion of chromosome 16.

Ten patients with acute myelomonocytic leukemia (AMML) and inversion of chromosome 16 who had CNS involvement were identified at M.D. Anderson Hospital between January 1972 and December 1984. The nervous system signs and symptoms were evaluated in detail. CT scans, CSF cytologies, and treatment modalities were reviewed. Two patients underwent biopsies of lesions that proved to be granulocytic sarcomas. AMML with inversion 16 carries a much higher (33%) incidence of CNS involvement in the form of leptomeningeal metastasis and/or granulocytic sarcoma than all other acute nonlymphocytic leukemias (5%). The reason for this appears to be related to the chromosomal aberration and not to prolonged survival.

Adult↗
PubMed1987

Clinical investigation of human alpha interferon in chronic myelogenous leukemia.

Fifty-one patients with previously untreated or minimally treated chronic myelogenous leukemia in chronic phase received human alpha interferon 3 to 9 X 10(6) units intramuscularly (IM) daily until complete hematologic remission, then at doses ranging from 3 X 10(6) units every other day to 9 X 10(6) units daily. Forty-one (80%) patients achieved a hematologic response, 36 (71%) of them attaining a complete hematologic remission with normal peripheral WBC and differential counts. Responding patients showed continuous but slow normalization of several other blood and marrow parameters including platelet counts, serum lactic dehydrogenase and B12 levels, and marrow cellularity and maturation index. Suppression of the Philadelphia chromosome on serial cytogenetic studies of marrow metaphases was documented in 20 of the 36 patients who achieved complete hematologic remission (56%; 39% of total group), eight of whom (22%) had a decrease of the Philadelphia chromosome-positive metaphases to less than 35%. These changes were persistent for 6 months or longer in 18 patients, seven of whom had continuous suppression of the Philadelphia chromosome to less than 90% for a median of 30+ months (range 21+ to 39+ months). After a median follow-up period of 37 months, 25 patients remain in continued disease control with interferon therapy. The projected 3-year survival rate is 76%, with a yearly death rate of 6%, 9%, and 9% in the first 3 years. Response, Philadelphia chromosome suppression, and survival were significantly better among patients in the low-risk category compared to intermediate- and high-risk categories, as defined by a multivariate analysis-derived prognostic model. The projected 3-year survival rate was 94% for patients who achieved a complete hematologic remission on interferon therapy and 45% for those who did not. Thirteen patients have developed blastic crisis, six with lymphoid and three with undifferentiated morphology. We conclude that human leukocyte alpha interferon effectively controls chronic myeloid leukemia and allows reappearance of diploid hemopoietic cells in some patients.

Aged↗
PubMed1987

The effect of long-term marrow culture on the nonadherent Philadelphia chromosome-positive clone in chronic myelogenous leukemia: preliminary observations.

To evaluate the effect of long-term culture on the Philadelphia chromosome-positive nonadherent hemopoietic clone in chronic myelogenous leukemia, bone marrow aspirates from five patients were grown in culture for three to four weeks. In addition to control cultures, samples were incubated with recombinant alpha-interferon. Cytogenetic studies performed on the nonadherent hemopoietic cells demonstrated suppression of the Philadelphia chromosome-positive clones, and appearance of cells with normal diploid karyotype in two of the five patients studied; cells from the remaining three patients showed persistent Philadelphia chromosome-positive cells in 100% of the metaphases. Exposure to alpha-interferon did not enhance the suppression of the Philadelphia chromosome-positive clones. A good correlation was noted between in vitro results and in vivo cytogenetic response: the two patients whose in vitro studies showed diploid clones achieved complete hematologic remission and suppression of Philadelphia chromosome-positive metaphases with therapy. Our data suggest that long-term culture favors the growth of normal clones over Philadelphia chromosome-positive clones in the nonadherent hemopoietic cells of some patients with chronic myelogenous leukemia. The value of the procedure as an in vitro predictive test for residual normal stem cells and response to therapy and for autologous marrow in vitro purging needs further exploration.

Adult↗
PubMed1986

Chronic myelogenous leukaemia: haematological remissions with alpha interferon.

Twenty-seven consecutive patients with previously untreated, or minimally treated benign phase Philadelphia-chromosome-positive, chronic myelogenous leukaemia (CML) were treated with partially purified human leucocyte (alpha) interferon; 24 of the 27 patients responded to therapy achieving either haematological remission (20 patients) or partial haematological remission (four patients). In the responding patients the peripheral white blood cells declined from a median of 89.6 X 10 X 10(9)/l to 4.5 X 10 X 10(9)/l. The serum lactate dehydrogenase declined from a mean of 8.36 Katal/l (492 mu/ml) to 2.8 Katal/l (165 mu/ml), and the vitamin B12 levels declined from 1492 pg/ml to 838 pg/ml. Fifteen patients had splenomegaly. The spleen size normalized in four and decreased by a median of 30% in 10 additional patients. The bone marrow cellularity fell from a median of 100% to a median of 62%. In seven of the 24 responding patients, followed for greater than or equal to 6 months, the percentage of Ph1-positive cells in the bone marrow declined to a median of 70% (range 5-75%). Alpha interferon was found to be an effective therapeutic agent for controlling the myeloid proliferation in CML, and in partially restoring the nonclonal haematopoietic cells in some of the patients.

Adult↗
PubMed1986

Piperazinedione, total body irradiation, and autologous bone marrow transplantation in chronic myelogenous leukemia.

Eleven patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in blast crisis (ten patients) or accelerated disease (one patient) were treated with piperazinedione (PIP) and fractionated total body irradiation (TBI) followed by autologous bone marrow transplantation (ABMT). Three patients were transplanted with marrow from which the Ph1 clone had been eradicated by prior intensive chemotherapy. All patients responded with disappearance of blasts in bone marrow and peripheral blood. Six patients achieved a second chronic phase lasting 3 to 14 months (median, 6 months). Two patients had incomplete recovery, and three patients failed to engraft and died from infection. Transplantation with Ph1-negative bone marrow did not improve response duration or survival. Recurrence of blast crisis and incomplete engraftment continue to be the two major problems in this patient group, and more active regimens need to be investigated.

Adult↗
PubMed1985

Intensive combination chemotherapy (ROAP 10) and splenectomy in the management of chronic myelogenous leukemia.

To investigate the role of intensive chemotherapy in chronic myelogenous leukemia (CML), we treated 37 patients who had Philadelphia-positive benign-phase disease with rubidazone 300 mg/m2/d 1 (or daunorubicin 30 mg/m2/d X 4), cytosine arabinoside 80 mg/m2/d X 10, vincristine 2 mg/d 1, and prednisone 100 mg/d X 5 (ROAP 10), every four weeks for a median of three cycles. This treatment was followed by splenectomy and by subsequent maintenance therapy with 1 to 5 g hydroxyurea daily in intermittent courses. After a median follow-up of 42 months (range, 24 to 54 months), 20 patients (54%) remain in benign phase. The projected median survival is 52 months, and the three-year survival rate is 67%. Six patients (16%) developed blastic crisis, and eight died in the benign phase. A significant cytogenetic response, defined as a fall in the percentage of Philadelphia-positive cells to less than or equal to 30%, occurred in 18 (53%) of 34 patients who had serial cytogenetic studies. Six patients (18%) had reductions to 35% to 90%, whereas ten remained 100% positive. Cytogenetic response lasted for a median of six months from the time of maximal response (range, 1 to 18 months). Blastic crisis or accelerated disease developed in seven (44%) of the 16 patients who manifested minimal or no cytogenetic response, compared to only two of the 18 patients (11%) who achieved a significant cytogenetic response. Toxicity, which resulted in one death, was due to myelosuppression and consisted of febrile episodes during neutropenia (24% of courses), documented infections (8% of courses), and bleeding (8% of courses). ROAP 10 intensive therapy produces moderate survival improvement for CML patients compared to a matched historical control group of patients treated at our institution, but it has considerable myelosuppressive toxicity. The Philadelphia chromosome response is an important treatment-related prognostic factor.

Adolescent↗
PubMed1985

A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22).

Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

Adult↗