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J M Flexner

Publications and source records attributed to J M Flexner.

At least 37 records · Page 2Linked to original sources
PubMed1986

Clinical experience with amphotericin B in acute myelogenous leukemia.

The empirical use of amphotericin B in febrile leukemic patients not responding to antimicrobial agents has previously led to a significant decrease in fatal fungal infections and a significant increase in complete remissions. In this series of 66 patients receiving induction therapy for acute myelogenous leukemia (AML), 49 (74%) received amphotericin B. The median interval between institution of antibiotics and amphotericin B was ten days. Fifteen patients had clinical evidence of fungal infection, but only two (3%) died of fungal infection during induction therapy for AML. We discontinued amphotericin B upon granulocyte recovery (greater than 500/cu mm) unless a pulmonary infiltrate was present. Even though only five of 15 patients with probable fungal infection received more than 1,000 mg of amphotericin B, no patient had recurrent fungal disease while in remission. The incidence of clinically suspected fungal pneumonia during consolidation therapy and reinduction therapy also suggested that our therapy was adequate. An increased incidence of late fungal pneumonia in patients receiving reinduction was associated with prolonged neutropenia (greater than 50 days). This study supports the empirical use of amphotericin B during induction therapy for AML, and suggests that doses can be smaller than those generally recommended for fungal infection.

Aged↗
PubMed1986

Non-Hodgkin's lymphoma after treatment of Hodgkin's disease: association with Epstein-Barr virus.

Non-Hodgkin's lymphoma occurs infrequently as a late complication of obscure cause after treatment of Hodgkin's disease. We investigated the possible role of Epstein-Barr virus in the pathogenesis of such secondary malignancies of B-cell lineage. Two patients, aged 25 and 43 years, developed high-grade non-Hodgkin's lymphomas 12 and 8 years after radiation therapy for Hodgkin's disease. Serologic profiles in these patients showed evidence of acute and past Epstein-Barr virus infections, respectively. Molecular hybridization analysis showed the presence of multiple cellular equivalents of virus genome in tumor specimens from each patient. Our findings suggest that Epstein-Barr virus may play an integral role in the pathogenesis of non-Hodgkin's lymphoma of B-cell lineage that develops after treatment of Hodgkin's disease.

Adolescent↗
PubMed1986

Modified cyclophosphamide, vincristine, methotrexate, leucovorin, and cytarabine (COMLA) in intermediate- and high-grade lymphoma: an effective short-course regimen.

Twenty-one patients with intermediate- and high-grade lymphomas were treated with modified cyclophosphamide, vincristine, methotrexate, leucovorin, and cytarabine (COMLA). This regimen utilizes the drugs used in COMLA in similar doses, but cyclophosphamide is given twice as frequently, cytarabine is given by continuous infusion, and the total duration of therapy is reduced to 16 weeks. Complete remission rates were 80% in patients with intermediate-grade lymphomas and 67% in patients with high-grade lymphomas. Persistent complete remission rates were 60% and 33%, respectively, with a median follow-up of 26 months for surviving patients. This regimen was myelotoxic, but there were no toxic deaths. Modified COMLA is a relatively nontoxic regimen producing excellent results in intermediate-grade lymphomas.

Actuarial Analysis↗
PubMed1985

Morphologic and immunologic evidence of composite B- and T-cell lymphomas. A report of three cases developing in follicular center cell lymphomas.

Composite lymphoma (CL) may be defined as two lymphomas, differing as to their cell of origin, that occur simultaneously in the same tissue specimen. While CL usually is indicated histopathologically by at least two morphologically distinct lymphomatous proliferations, the proof that these proliferations are separate and distinct neoplasms requires immunologic analysis. Many so-called cases of CL actually represent the well-known phenomenon of lymphoid transformation, in which there is a small cell and a large cell component in the same specimen. Immunologic studies in these cases have shown that the cytologically distinct neoplastic cells represent different stages in the same cell line. While studying a large series of follicular center cell (FCC) lymphomas, the authors recognized three cases in which there was both morphologic and immunologic evidence of a true CL. Following an initial diagnosis of a nodular FCC lymphoma, rebiopsies from 21 to 62 months later showed the coexistence of a nodular FCC (B-cell) component and a diffuse large cell (T-cell) component.

Adult↗
PubMed1985

Improved survival in adult acute lymphoblastic leukemia. Need for more effective CNS prophylaxis.

Using a multimodality approach to adult acute lymphoblastic leukemia, 93% of patients achieved a complete remission; among patients achieving a complete remission, 43% are predicted to remain disease-free for 5 years. Despite use of cranial irradiation (2400 rad) and intrathecal methotrexate (12 mg X 5), CNS relapse occurred in 5/14 patients (36%). With improved systemic therapy of adult ALL, survival is increased and "standard" CNS prophylaxis is not as effective as it appeared to be when systemic remissions were of shorter duration. More effective approaches to CNS prophylaxis need to be devised.

Actuarial Analysis↗
PubMed1985

A slab of meat.

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Brain Neoplasms↗
PubMed1985

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study.

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.

Acute Disease↗
PubMed1984

Malignant lymphomas of follicular center cell origin in humans. V. Incidence, clinical features, and prognostic implications of transformation of small cleaved cell nodular lymphoma.

Seventy-five cases of small cleaved cell nodular lymphoma (SCC-N) were reviewed. Thirty-four cases underwent repeat biopsy a median of 54 months after diagnosis (range, 7-116 months) because of progressive or recurrent disease. Histologic conversion to a transformed (noncleaved) cell lymphoma was found at re-biopsy in 13 of 34 cases (38%). Neither age, gender, stage, visceral sites of disease, nor symptoms at presentation were predictive of subsequent conversion. Similarly, none of the clinical features analyzed at the time of rebiopsy were predictive of whether the rebiopsy would show stable histology or transformation. Documentation of transformation was of significant prognostic value. Although rebiopsies were performed at the time of progressive disease, survival following re-biopsy was 37.5 months for patients found to have cleaved cell lymphoma at re-biopsy, and only 2.5 months for those with transformed cell lymphoma at re-biopsy. Two of the cases which had immunoglobulin surface markers studied at diagnosis and at transformation, showed retention of heavy and light chain markers. This implies that the change in appearance involves the original neoplastic clone and was not due to a second neoplasm. Development of transformed cell lymphoma is one of the most common features of the aggressive phase of indolent lymphoma. Repeat biopsy in all patients with indolent lymphoma who have relapsing or progressive disease is recommended.

Adult↗
PubMed1984

Idiopathic thrombocytopenic purpura during remission of thrombotic thrombocytopenic purpura.

Three patients were treated empirically with anti-platelet agents, prednisone, plasmapheresis, and prostacyclin for the classical clinical syndrome of thrombotic thrombocytopenic purpura (TTP). All three patients initially responded, then relapsed after one to 13 months with a clinical picture characteristic of immunogenic thrombocytopenic purpura (ITP). At relapse, all three had thrombocytopenia without microangiopathy or other causes of thrombocytopenia. All responded to splenectomy. This complication of TTP may become more common with improved survival in TTP. Recognition may prevent inappropriate therapy.

Adolescent↗
PubMed1984

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases.

Clinical and histopathologic material from 42 patients with peripheral T-cell lymphoma (PTCL) was reviewed. The median age was 63.5 years (range, 11-97 years). The male:female ratio was 2.8:1. Prior immune or lymphoproliferative diseases occurred in 36% of the patients. PTCL was advanced at presentation with B symptoms (67%), generalized adenopathy (69%), and stage III/IV disease (79%). Suspected lung or pleural involvement (21%), hepatomegaly (29%), and splenomegaly (43%) were common; marrow involvement was documented in 37% of the patients at presentation and in 51% of patients during the illness. Hypercalcemia and eosinophilia occurred in 19% and 29% of patients, respectively. Among patients receiving combination chemotherapy (BCOP, CHOP, BACOP, COMLA), eight (24%) of 33 achieved a complete remission and only four (12%) of 33 had a sustained complete remission. The median survival for PTCL was 11 months. Because of the poor response to standard therapy, clinical trials should identify cases of PTCL and evaluate newer regimens in this subset of aggressive lymphoma.

Adolescent↗
PubMed1983

Malignant lymphoma of follicular center cell origin in humans. IV. Small transformed (noncleaved) cell lymphoma of the non-Burkitt's type.

Small transformed cell lymphoma (STC) is the least common follicular center cell neoplasm in the Lukes-Collins classification system. If the cells are homogenous in size and shape, Burkitt's lymphoma (STC-BL) is diagnosed; otherwise STC lymphoma of the non-Burkitt's type (STC-nBL) is present. The authors have reviewed their experience with 17 cases of STC-nBL. This neoplasm affects all ages, both sexes equally, and most commonly is Stage IV based either on a visceral abdominal mass or bone marrow involvement. Surface immunoglobulin analysis revealed IgM in all cases tested. In spite of aggressive treatment protocols, there were only 5 of 17 (29%) clinical complete responses. Four of these five have continuous remission from 8 to 23 months after diagnosis; all four of these patients were treated with regimens containing high-dose cyclophosphamide. Future analyses including viral studies, chromosomal analyses, and uniform treatment protocols will help determine whether STC-nBL and Burkitt's lymphoma are truly distinct entities.

Adolescent↗
PubMed1983

Gastrointestinal involvement in lymphomatoid granulomatosis. Report of a case review of the literature.

Lymphomatoid granulomatosis is a lymphoproliferative process affecting multiple organ systems usually including the lungs. Significant gastrointestinal involvement, however, has rarely been reported. Pathologic examination reveals a vasocentric polymorphous lymphoid infiltrate. A case of lymphomatoid granulomatosis with gastrointestinal manifestations necessitating aggressive surgical intervention is reported. The clinical presentation, pathologic features, and various aspects of therapy of lymphomatoid granulomatosis involving the gastrointestinal tract are discussed.

Adult↗
PubMed1982

Clinical value of empirical amphotericin B in patients with acute myelogenous leukemia.

From August 1977 to October 1978, 23 patients with acute myelogenous leukemia (AML) received induction therapy at Vanderbilt University Hospital. Six patients died of documented fungal infection, predominantly aspergillus pneumonia; the complete remission rate was only 40%. Based on this experience we began using amphotericin B empirically in any AML patient remaining febrile or having recurrent fever after a week of broad spectrum antibiotics. Of 22 patients treated from October 1978 to August 1980, none died of fungal infection during induction therapy; the remission rate increased significantly to 77%. Chemotherapy and supportive care were otherwise unchanged during this period. While the first group was older, the improvement in remission rate was also seen in patients younger than 60 years of age. Since fungal infection may be difficult to document, this study suggests that empirical amphotericin B is reasonable therapy in leukemic patients remaining febrile or having a recurrent fever following a week of broad spectrum antibiotics, if the institution has a high incidence of fungal infections.

Adult↗
PubMed1982

Effective multidrug, multimodality consolidation therapy of adult acute lymphocytic leukemia: a preliminary report.

Twelve of 13 adult patients with acute lymphocytic leukemia, acute undifferentiated leukemia, or convoluted T-cell lymphoma (T-cell ALL) who were treated with Adriamycin, vincristine, and prednisone achieved a complete remission. An intensive consolidation regimen was administered. This regimen included Cytosine Arabinoside, L-asparaginase, and multiple courses of CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone). In addition, cranial irradiation and intrathecal methotrexate were administered. By actuarial estimate, 81% of previously untreated patients who achieved a complete remission will remain in remission for more than two years.

Adult↗
PubMed1982

Anatomic substages of stage IIIA Hodgkin's disease: followup of a collaborative study.

The clinical significance of anatomic substage was reassessed in a previously reported series of 130 patients with Hodgkin's disease in pathologic stage IIIA. For 100 patients, followup was greater than 8 years. By definition, stage III1 disease includes involvement of spleen or splenic, celiac, or portal nodes, or any combination of these; stage III2 disease includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Both 8-year relapse-free survival (71% versus 40%) and 8-year overall survival (80% versus 54%) were better in stage III1A than in III2A patients (P less than 0.001). For stage III1A, relapse-free survival was better in patients receiving radiotherapy alone as initial treatment (92% versus 60%, P less than 0.002). However, 8 year overall survival rates in these two treatment groups were not significantly different (88% versus 76%, P = 0.20). For stage III2A, both relapse-free survival at 8 years (84% versus 19%, P less than 0.001) and overall survival at 8 years (84% versus 41%, P less than 0.01) were superior in patients receiving combined modality therapy. Anatomic substage is a critical prognostic variable, especially if standard total nodal radiotherapy is considered as one of the therapeutic options.

Adult↗
PubMed1980

Acute leukemia of adults. Ultrastructural, cytochemical and histologic observations in 100 cases.

In order to establish guidelines for categorization of acute leukemia, marrow histology, special stains, and electron microscopy were performed in 100 adult leukemia cases. Differential counts for each stain were performed, and the results were combined with those obtained by electron microscopy for final classification. Myeloid (non-lymphoid) leukemia was most common (83 cases), and there were 13 lymphoid cases, two cases of erythroleukemia, and two undifferentiated leukemias. Histologic studies of marrow particles revealed significant admixtures of lymphocytes, plasma cells, and abnormal erythroid elements, particularly in acute myelomonocytic leukemia. Interpretations of cytochemical results were confirmed by ultrastructural studies in 90% of the cases. Clinically significant discrepancies between cytochemical and ultrastructural interpretations were rarely found. Only two myeloid and five lymphoid cases did not mark typically with any cytochemical stain. The single most reliable special stain was the periodic acid-Schiff stain, whereas the stain most difficult to interpret was the alpha-naphthyl acetate esterase stain. Sudan black stain was particularly helpful in demonstrating Auer rods. Five of six cases unclassified by cytochemistry were categorized by electron microscopy. Although patterns of cytochemical staining were delineated for each type of leukemia, significant intragroup variation in cytochemical reactions was recognized. This study indicates that ultrastructural examination should be routinely used for categorization of cases with equivocal cytochemical findings and for analysis of unclassified cases.

Adolescent↗
PubMed1980

Chronic myelogenous leukemia: a 22-year survival.

A 25-year-old woman presented with classic features of chronic myelogenous leukemia. After 15 months of control with splenic irradiation, rising blood counts necessitated busulfan therapy, producing severe thrombocytopenia which persisted for nearly three years. The patient has remained in complete remission without therapy for 17 years and has now survived 22 years since diagnosis during which blood counts and results of bone marrow examinations and marrow chromosome studies have been normal.

Adult↗