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Biomedical subjects

F S Morrison

Publications and source records attributed to F S Morrison.

At least 19 recordsLinked to original sources

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study.

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

Adult

Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance.

Between August 1978 and September 1982, 642 patients with newly diagnosed acute myelogenous leukemia (AML) were entered onto a Southwest Oncology Group Study which addressed four questions. (i) What is the comparative utility of rubidazone versus adriamycin in remission induction? (ii) What is the role of prophylactic intrathecal therapy in AML? (iii) Does late intensification affect treatment outcome? (iv) Does maintenance with levamisole affect disease-free survival or overall survival? Among 611 evaluable patients, 329 (54%) achieved complete remission. There was no difference in the remission rate between those patients receiving rubidazone (54%) and those receiving adriamycin (54%) as part of the induction regimen. Prophylactic intrathecal therapy with cytosine arabinoside had no effect on the incidence of central nervous system disease or survival. After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone). T patients randomized to late intensification had better survival and disease-free survival, compared to those randomized to receive no late intensification (p = 0.027 and 0.030, respectively). At twelve months of remission, surviving patients were randomized to receive levamisole or no further treatment. There was no evidence that levamisole affected survival or disease-free survival.

Antineoplastic Combined Chemotherapy Protocols

Use of continuous flow erythrocytapheresis in pregnant patients with sickle cell disease.

The role of partial prophylactic red cell exchange transfusion in the management of pregnant patients with major sickle hemoglobinopathies is unclear. Over a 10-year period, 131 pregnant patients with major hemoglobinopathies (HbS 101, HbS-C 30) were managed by the same group of physicians. Of these, 103 received partial prophylactic exchange transfusion early during prenatal care while 28 received blood only when serious complications developed (control group). Patients treated with exchange transfusion received continuous flow erythrocytapheresis on an outpatient basis. The results indicate that there were fewer crises (P = .0001), a reduction in other significant medical complications (P = .002), and a decrease in maternal hospital days (P = .05) in those receiving prophylactic transfusions compared to women in the control group. The number of preterm deliveries (P = .004), the prevalence of low birthweight infants (P = .01), and the perinatal death rate (P = .01) were significantly lower among those who were routinely transfused. Two patients developed hepatitis, five had transfusion reactions, and 11 were found to have alloantibodies among those receiving prophylactic transfusions versus one, two, and five patients, respectively, in the control group. The results indicate a benefit of this methodology in the treatment of pregnant sickle cell patients in our population. However, a national collaborative randomized study is needed to adequately address the controversy regarding the use of red cell exchange in the pregnant sickler.

Adolescent

Pathogenetic implications of internuclear bridging in myelodysplastic syndrome. An Eastern Cooperative Oncology Group/Southwest Oncology Group Cooperative Study.

Numerous morphologic features have been described in bone marrow and peripheral blood in myelodysplastic syndrome (MDS). We draw attention to a high incidence of a subtle morphologic feature, internuclear bridging (INB), not previously recognized as a morphologic feature in MDS. The occurrence of INB in MDS suggests an underlying abnormality of mitotic division that could explain the impaired production of hematopoietic cells, the addition and deletion cytogenetic changes, and the stepwise disease progression and cytogenetic progression characteristic of MDS. Lack of awareness that INB occurs in MDS may cause confusion of MDS and congenital dyserythropoietic anemia type I, a congenital process also characterized by INB.

Bone Marrow

Transient acquired factor X deficiency: report of the use of activated clotting concentrate to control a life-threatening hemorrhage.

Acquired deficiency of factor X is an uncommon occurrence. It has usually developed in association with amyloidosis [8] and, in that setting, it has been irreversible. Transient deficiency appears to be associated with an acute respiratory infection in the majority of cases. Bleeding in these patients can be life-threatening and has been difficult to control. Konyne produces a brief correction of the prothrombin time and an elevation in the factor X level, but has not been effective in stopping bleeding. We report the first successful correction of prothrombin time and clinical resolution of bleeding attending the use of Autoplex T. If bleeding persists after appropriate specific factor replacement and the clinical condition warrants, the use of Autoplex T (activated prothrombin complex) deserves prompt consideration.

Aged

Thrombotic thrombocytopenic purpura and pancreatitis.

Abdominal pain is frequently encountered in patients with thrombotic thrombocytopenic purpura (TTP). Often the pain is secondary to inflammation of the pancreas. A case is presented in which the usual signs of TTP developed well after the clinical and laboratory demonstration of pancreatitis, raising the possibility that the pancreatic inflammation triggered the onset of TTP. Treatment with plasmapheresis resulted in prompt improvement. TTP should be considered in patients with abdominal pain or pancreatitis in whom thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, fever, and renal disease are present.

Female

Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study.

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.

Antineoplastic Agents

Spleen size and chromosome analysis as prognostic factors in chronic myelogenous leukemia.

Of 72 patients with chronic myelogenous leukemia (CML), 37 were Ph1 positive, eight were negative, and 27 were not evaluated for the Ph1 chromosome. Of the 37 patients positive for Ph1, 31 had adequate evaluation. These 31 patients were reviewed for survival with reference to spleen size. Seventeen patients with spleens 3 cm or less below the left costal margin had a 50% survival of 75 months, with a mean survival of 53.9 months. Fourteen patients with spleens greater than 3 cm below the left costal margin had a 50% survival of 21 months, with a mean survival of 19 months (P = .0014). It is concluded that small splenic size in CML is associated with longer survival. It may be that this observation should be taken into consideration when considering splenectomy in the management of patients with CML.

Adolescent

Septicemia during antibiotic therapy in neutropenic patients.

Two patients with acute leukemia developed septicemia while receiving antibiotic therapy. In both cases, the microorganism grown from the blood was sensitive to the drugs the patients were receiving. Areas of colonization by the same organisms were found at autopsy in the necrotic spleen and in the necrotic colonic mucosa. Septicemia developing during antibiotic therapy can indicate colonization of necrotic organs and appropriate diagnostic and therapeutic measures may be necessary.

Adult

Acute megakaryocytic leukemia. Description of a case initially seen as preleukemia syndrome.

A 52-year-old man had aregenerative anemia unresponsive to pyridoxine hydrochloride. Acute leukemia developed, and he died four months after diagnosis. At autopsy he had acute megakaryocytic leukemia with involvement of bone marrow, liver, spleen, adrenals, kidneys, and thyroid. Chromosomal analysis revealed absence of both diploid and Ph1 chromosomes. A mode of 45 chromosomes and aneuploidy were present. This is similar to the only other case with chromosomal studies. Of the 15 acceptable documented cases, eight were men and seven were women. Their age varied from 28 to 76 (mean, 55) years. Only two were less than 40 years of age. Most had pancytopenia, and all were dead within six months of diagnosis.

Autopsy

5-azacytidine in acute leukemia.

101 patients with acute leukemia in relapse were treated with 5-azacytidine according to three schedules: Regimen A--300 mg/m2(day divided intravenously at 8 hour intervals for 5 days; Regimen B--750 mg/m2 as a single iv pulse dose administered at 2 to 3 weeks intervals; and Regimen C--300 mg/m2/day by continuous infusion daily for 5 days. Twelve patients achieved a complete remission (CR) and six achieved a partial remission (PR) for an overall 18% response rate. Of 78 patients receiving an adequate trial the response rate was 23%. An average of 1.5 courses and a median of 5 weeks were necessary to achieve a response. The median duration of CR patients was 21 weeks and for PR patients it was 5 weeks. Response rates were 24% for Regimen A, 0 for Regimen B, and 1 of 8 for Regimen C. The CR rate for AML and AMML was 13%. Two of eight AMoL patients achieved a CR. Only 2 of 23 ALL patients responded, one of whom achieved a CR. Toxicity included moderate to severe nausea and vomiting, diarrhea, stomatitis, skin rash, and prolonged myelosuppression. 5-azacytidine has significant activity in the acute nonlymphoblastic leukemias.

Acute Disease

Combination chemotherapy using cyclophosphamide, vincristine, methotrexate, 5-fluorouracil, and prednisone in solid tumors.

Three hundred and ninety-eight patients with disseminated solid tumors other than breast cancer, were treated with a combination chemotherapy protocol utilizing cyclophosphamide, vincristine sulfate, methotrexate, 5-fluorouracil, and prednisone. Three hundred and eighty were evaluable (95.5%). Partial or complete tumor regressions were noted in 73 of 380 (19%) evaluable patients. Response to therapy was associated with a prolongation and survival. The largest tumor categories were lung, ovary, and gastrointestinal. The proportion of complete plus partial responses in evaluable lung cancer patients was 40/236 (17%), compared to 20/44 (45%) for ovarian cancer patients and 6/39 (15%) for gastrointestinal tumors. Of the patients who could be evaluated for toxicity, 47% had minimal or no toxicity, 51% had moderate to severe toxicity, and 2% had life threatening toxicity. Virtually all patients were treated and managed as outpatients.

Cyclophosphamide

Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5-FU vs. methyl-CCNU plus bolus weekly 5-FU. A Southwest Oncology Group study.

In a randomized and stratified study, 294 patients with advanced gastrointestinal cancer were treated either with 5-fluorouracil (5-FU) 400 mg/m2 weekly intravenously (i.v.) or 5-FU 400 mg/m2 i.v. weekly plus methyl-CCNU 175 mg/m2 orally (p.o.) every 6 weeks. The response rate in colorectal cancer with 5-FU was 9.5% while the two-drug treatment produced a response of 31.8% (p=.009). The response in all gastrointestinal cancers to 5-FU was 10.6% as compared with29.3% for the combination (p=.012). All responses were partial. The two-drug regimen is more effective and more toxic than weekly 5-FU therapy.

Adolescent