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Biomedical subjects

J M Flexner

Publications and source records attributed to J M Flexner.

At least 19 recordsLinked to original sources
PubMed1991

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma.

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (greater than 300 IU/l), 43%; and bulky (greater than 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 IV on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (less than 1000/microliters) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Adult↗
PubMed1991

Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma.

Thirty-one patients were diagnosed by morphologic and immunophenotypic features as having primary Ki-1 anaplastic large-cell lymphoma (Ki-1 ALCL). the median age was 35 years (range, 4 months to 78 years); the male:female ratio was 18:13. B symptoms were observed in 13 patients. Peripheral adenopathy was present in 26 patients, while mediastinal adenopathy occurred in five. There was extranodal disease in 13 patients; the most common extranodal site was skin with seven affected. Seventeen patients had stage III/IV disease. Immunophenotypes were T cell in 24 patients and B cell in four patients; immunophenotype could not be determined in three patients. Cytogenetic abnormalities in chromosomes 2, 5, and 7 were detected in three patients. Although therapy was heterogeneous, the actuarial 2-year survival was 73%. Two-year disease-free survival was 39% for all patients; for stages I and II, it was 62% compared with 20% for stages III and IV (P = .001). Complete remission (CR) occurred in 21 of 23 patients receiving combination chemotherapy; however, nine relapses, including six of seven stage IV patients, occurred within 21 months of diagnosis. Preliminary observations suggest that Ki-1 ALCL may have a quiescent phase in the rare patient with only localized skin disease. However, the disease generally behaves as an intermediate- to high-grade lymphoma, and patients with Ki-1 ALCL should receive curative-intent combination chemotherapy.

Actuarial Analysis↗
PubMed1991

Hemochromatosis: diagnosis and treatment.

What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Large-cell lymphomas: clinical and prognostic features.

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.

Actuarial Analysis↗
PubMed1990

The thin red line.

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Anecdotes as Topic↗
PubMed1989

High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results.

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.

Adolescent↗
PubMed1988

Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Adult↗
PubMed1988

Nephrotoxicity in leukemic patients receiving empirical amphotericin B and aminoglycosides.

Twelve leukemic patients (19%) receiving amphotericin B and aminoglycosides had nephrotoxicity (creatinine value greater than 2.0 mg/dl). Patients with nephrotoxicity tended to be older than patients without nephrotoxicity; gender and total amphotericin B dose were not related to nephrotoxicity. Sodium administration has previously been shown to reverse amphotericin B nephrotoxicity. In this series, among patients receiving ticarcillin at greater than or equal to 18 gm/day (93.6 mEq of sodium per day) the incidence of nephrotoxicity was significantly decreased (1/30, or 3.3%). A multivariate analysis showed that this protective effect of ticarcillin was not dependent on the fact that patients receiving ticarcillin were less likely to receive vancomycin. There were insufficient patients receiving sodium in the absence of ticarcillin to study the effect of sodium alone. However, our observations are consistent with the hypothesis that sodium can prevent renal dysfunction in this clinical situation.

Adult↗
PubMed1988

Plasmacytic neoplasm of the gastrointestinal tract in a patient with long-standing monoclonal gammopathy.

We have reported the 21-year follow-up of a patient with progressive monoclonal IgG lambda gammopathy and recurrent pneumococcal infections who had diarrhea and weight loss. The serum IgG had risen from 2,850 mg/dl in 1966 to 6,120 mg/dl in 1986, but repeated evaluations had shown no evidence of myeloma or lymphoma. Evaluation revealed infiltration of the gastrointestinal tract by a plasmacytic malignancy with a surface heavy and light chain identical to her serum monoclonal band.

Bone Marrow Examination↗
PubMed1988

Non-Hodgkin's lymphoma of the gastrointestinal tract: an analysis of clinical and pathologic features affecting outcome.

Clinical and histopathologic data from 87 patients with primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract diagnosed between 1974 and 1984 were reviewed. B-cell lymphomas of intermediate- or high-grade histology constituted 78% of lesions. Stage of disease varied with histologic grade, with a preponderance of advanced disease (stages IIIE and IV) in patients with low-grade lymphoma (15 of 21) (71%), compared with higher grade lesions (38%, P = .01). Among patients with nonlocalized (stages IIE through IV) lymphoma of intermediate- or high-grade histology, surgical resection of the primary focus afforded a higher rate of complete remission (CR) (70% v 50%) and sustained CR (61% v 21%, P = .04) after cytotoxic therapy compared with the nonresected cohort. The median survival in the resected group was 51 months + compared with 13 months in the nonresected patients (P = .012). Differences in outcome were attributable to a high risk of treatment-related complications (perforation and/or hemorrhage) (43% v 0%, P = .001) and local relapse (29% v 4%, P = .05) in nonresected individuals. Life-threatening local complications were not observed in patients with low-grade lymphoma managed solely with medical therapy. Histologic findings from surgically staged patients identified presence of extravisceral disease and intermediate- or high-grade tumor histology as features predictive of transmural invasion, enabling potential identification of patients who might be optimally managed by resection of the primary GI focus before initiation of cytotoxic therapy.

Adolescent↗
PubMed1987

Malignant lymphomas of follicular center cell origin in man. VI. Large cleaved cell lymphoma.

Between 1970 and 1986 61 patients with large cleaved cell lymphoma (LCCL) were observed and treated. Median age was 56, and there were slightly more women than men (ratio, 1.4:1). Forty-four cases (72%) had both a nodular and diffuse pattern; eight cases were nodular; nine cases were diffuse. Forty-three patients (70%) had Stage III or IV disease; four patients were Stage I (7%); 14 were Stage II (23%). Bone marrow was involved in 15 of 56 evaluable patients (27%). The median survival was 57 months. It was significantly shorter in symptomatic patients (median, 20 months) than in asymptomatic patients (median, 66 months; P = 0.002). Survival time was also shorter in Stage III and IV patients (median, 46 months) compared with Stage I and II patients (median, 100+ months; P = 0.032). Survival was independent of the disease pattern, marrow involvement, age, gender, and surface immunoglobulin heavy or light chain. Among Stage III and IV patients, survival was the same in patients who received therapy initially and in those who were treated expectantly. Among 10 advanced-stage patients who did not initially receive therapy, the median time to beginning therapy was 17 months; five patients received no therapy for 40 to 96 months. Among 14 advanced-stage patients receiving therapy regarded as curative in aggressive lymphoma, 50% experienced a complete remission (CR). However, unlike other aggressive large cell lymphomas, long-term, relapse-free survival was observed in only 9% of patients as the majority of CRs were associated with relapse rather than cure. Despite the fact that it is a large cell lymphoma, LCCL is best regarded as an indolent lymphoma.

Adult↗
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↗