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Biomedical subjects

J Cuttner

Publications and source records attributed to J Cuttner.

At least 55 records · Page 3Linked to original sources
PubMed1984

Evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies of patients with clonal hematopoietic neoplasia.

The origin and nature of cells forming the in vitro microenvironment in long-term cultures of human marrow were studied in five patients with clonal myeloproliferative disorders who were heterozygous for glucose-6-phosphatase dehydrogenase (G6PD). The results showed that cells in the adherent stromal layer forming the in vitro microenvironment were derived from the same clonal progenitors involved by the neoplasm in the four patients whose diseases originated in multipotent stem cells. In contrast, stromal cells were derived from normal progenitors in a patient with acute non-lymphocytic leukemia whose clone showed differentiative expression confined to cells in the granulocytic lineage. Mixing experiments demonstrated that the G6PD type displayed by the adherent marrow stromal cells was not obscured by contaminating non-adherent hematopoietic cells or marrow fibroblasts. The data suggest the existence of a pluripotent cell in normal hematopoiesis that gives rise to hematopoietic cells and to their micro-environment.

Adult↗
PubMed1984

Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by cancer and leukemia group B.

The efficacy of the addition of intensive therapy with daunorubicin (45 mg/m2 IV on days 1, 2, 3) to an otherwise identical induction program consisting of vincristine, prednisone, and L-asparaginase was assessed in 177 previously untreated adults (greater than or equal to 20 years of age) with acute lymphocytic leukemia (ALL). In the prospectively randomized phase of the investigation, 46 patients received daunorubicin in induction, whereas 53 did not. The two groups were otherwise comparable for pretreatment variables. A complete response was observed in 38/46 patients (83%) treated with daunorubicin, compared to 25/53 (47%) induced with vincristine, prednisone, and L-asparaginase alone (P = .003). The high response rate attributable to the use of the anthracycline was confirmed by the nonrandomized treatment of 78 subsequent patients, in whom a complete response rate of 76% was attained. A common program for central nervous system therapy and for maintenance therapy was employed in 103 patients achieving complete response. Maintenance consisted of cycles of 6-mercaptopurine (6-MP) and methotrexate with periodic reinforcement with vincristine and prednisone. Maintenance therapy proved to be minimally toxic. The average duration of complete response was 15 months and was not affected by the induction program employed. Approximately 25% of responders are projected to remain in continuing complete response for 36 months. The failure of the daunorubicin-containing programs to produce a higher percentage of long-term survivors, despite the higher complete response rates achieved, was thought to be due to the use of a maintenance program that was weak in intensity and dependent on reinforcement with vincristine and prednisone. These data clearly establish the increased effectiveness of vincristine, prednisone, L-asparaginase, and daunorubicin, as compared to this combination without daunorubicin, in the induction of complete response in adults with ALL. The results support the concept of an intensive, rather than a conservative, chemotherapeutic approach as the most appropriate strategy for the treatment of adult ALL.

Adult↗
PubMed1984

Mitoxantrone as a single agent and in combination chemotherapy in patients with refractory acute leukemia.

A total of 47 patients with relapsed or primarily refractory leukemia were treated with mitoxantrone alone or in combination with vincristine sulfate and prednisone or cytarabine. Eligible patients included those with adequate renal and hepatic function, normal left ventricular ejection fraction, and those who had received previous treatment. When mitoxantrone was given alone in a once daily times five schedule, 5 of 12 acute lymphoblastic leukemia patients achieved complete remission; 4 of these patients had been refractory to reinduction and 1 to induction chemotherapy with anthracycline-containing treatments. Four of these patients had progressive disease, and three died during induction. Of 12 patients with acute myeloid leukemia, 1 had a complete remission, 1 had a partial remission, 8 had progressive disease, and 2 died during induction. Mitoxantrone was also found to be active in two patients in the blastic transformation of chronic myeloid leukemia with a response in one patient lasting 17 weeks. Combinations of mitoxantrone with vincristine sulfate and prednisone resulted in complete remission in four of nine acute lymphoblastic leukemia patients and one of four patients with Tdt-positive chronic myeloid leukemia in blast crisis. Three of these patients had not experienced a prior remission following anthracycline-containing treatments. Partial remission occurred in two of the acute lymphoblastic leukemia patients and one of the Tdt-positive chronic myeloid leukemia patients. Two of this latter group of patients died in induction. Treatment with mitoxantrone and cytarabine resulted in two acute myeloid leukemia patients achieving complete remission and one a partial remission; two patients had progressive disease, and one died in induction. No response was seen in a patient with Tdt-negative chronic myeloid leukemia after two courses of treatment. One patient with acute leukemia in the course of myelofibrosis died in induction. All the patients achieving complete remission are alive and have been in complete remission from 2 to 12 months. Side effects included mild nausea and vomiting in 9 of 13 patients treated with the mitoxantrone-vincristine sulfate-prednisone combination, and in 3 of 8 patients treated with the mitoxantrone-cytarabine combination. Other side effects of the combination treatments include drug-induced oral mucositis (of a lesser degree than with mitoxantrone alone), transient hepatic abnormalities, and infectious complications, such as sepsis, Candida sp colonization of the upper digestive tract, and soft tissue cellulitis, in a few patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1984

TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings.

Thirteen patients with acute leukemias that were difficult to classify by the use of cytochemical staining and terminal deoxyribonucleotidyl transferase (TdT) activity are reported. The phenotype of the leukemic cells was characterized by the presence of mature or early monocyte lineage antigens and intense Ia antigen expression detected by monoclonal antibodies, terminal deoxytransferase activity, and cytochemical features, including both Sudan black B and periodic acid-Schiff activity. The mean age of this group of patients was 60 years. Five patients had leukemia occurring after chemotherapy or radiotherapy of a prior malignant disease, and two patients had a refractory anemia prior to development of acute leukemia. These patients had a low response rate to chemotherapy. This series of leukemia appears to form a distinct nosologic entity, representing a leukemic transformation among early cells of the monocyte lineage, resulting in a predominant neoplastic cell that is less mature than either the French-American-British M4 acute myelomonocytic leukemia or M5 acute monoblastic leukemia. The presence of terminal deoxytransferase activity was interpreted as indicating the primitive state of the cells in the differentiation sequence, rather than as implying any significance with respect to lineage.

Acute Disease↗
PubMed1983

Therapeutic leukapheresis for hyperleukocytosis in acute myelocytic leukemia.

Twenty-two patients with newly diagnosed acute myelocytic leukemia (AML) and white cell counts (WBC) greater than 100,000/microliters received one, two, or three leukaphereses prior to induction chemotherapy with cytosine arabinoside (Ara-C) and daunorubicin (DNR). Fifteen of 22 (68%) achieved a complete remission. Greater than a 30% decrease in initial WBC was found to be an important predictor of response. Fifteen of 17 patients (88%) with greater than 30% reduction of initial WBC achieved remission, while none of 5 patients with less than a 30% reduction responded (P = 0.001).

Adolescent↗
PubMed1983

Association of susceptibility to certain hematopoietic malignancies with the presence of Ia allodeterminants distinct from the DR series; utility of monoclonal antibody reagents.

The Ia antigen allospecificities of individuals with either B type chronic lymphocytic leukemia or hairy cell leukemia resembled one another and differed significantly from those of a control population. In contrast, the Ia alloantigens of individuals with non-Hodgkin's lymphoma were distinctly different from those of the leukemic group but differed little from the control group. A monoclonal antibody, IVD12, directed to an MB3-like determinant reacted with the greatest proportion of the leukemic individuals and yielded the highest positive relative risk. A lower degree of positive association was found with the presence of the MT2 determinant. In contrast, the low observed frequency of the MT1/MB1 determinant among leukemic individuals was associated with the most significant negative relative risk. The relative risk associated with the presence of DR5 was positive, while among patients with chronic lymphocytic leukemia the relative risk associated with DR2 was negative. Among patients with Hodgkin's Disease the relative risk associated with the presence of DR5 was significantly increased.

Antibodies, Monoclonal↗
PubMed1983

Mitoxantrone in patients with acute leukemia in relapse.

Twenty-six patients with acute leukemia in relapse were treated with mitoxantrone (dihydroxyanthracenedione dihydrochloride). The drug was given as a rapid i.v. infusion for 5 days, and doses were escalated from 8 mg/sq m daily for 5 days to 20 mg/sq m daily for 5 days. Five of 12 patients with acute lymphoblastic leukemia were induced into complete remission; one patient was induced into complete remission twice. The marrow response lasted from 3 to 50+ weeks. Among 12 patients with acute myelogenous leukemia, there was one complete and one partial remission, with response duration lasting 8 and 2 weeks. One patient with chronic myelogenous leukemia in blastic crisis also had a partial remission lasting 17 weeks. Remissions occurred at doses ranging from 8 to 14 mg/sq m daily for 5 days. All responders had been treated previously with anthracyclines. Drug-induced side effects included dose-limiting oral mucositis, sporadic nausea and vomiting, and transient elevations of the hepatic enzymes. Approximately one-third of the patients had septic complications during the myelosuppressive phase following treatment. We believe that mitoxantrone has definite utility in the treatment of acute leukemia in relapse.

Acute Disease↗
PubMed1982

Association of certain Ia allotypes with the occurrence of chronic lymphocytic leukemia. Recognition by a monoclonal anti-Ia reagent of a susceptibility determinant not in the DR series.

The Ia antigen allospecificities of individuals with B type chronic lymphocytic leukemia differed significantly from those of a control population. A monoclonal antibody, IVD12, directed to a MB3-1ike determinant, reacted with 92.5 percent of the individuals with leukemia and yielded the greatest positive relative risk, 13.5. A lower degree of positive association was found with the presence of the MT2 determinant. In contrast, the low observed frequency of the MT1/MB1 determinant among leukemic individuals was associated with the most significant negative relative risk, -8.1. Among HLA- DR specificities, the relative risk associated with the presence of DR5 was positive while that with DR2 was negative.

Adult↗
PubMed1982

Comparison of oral melphalan, CCNU, and BCNU with and without vincristine and prednisone in the treatment of multiple myeloma. Cancer and Leukemia Group B experience.

A total of 361 evaluable patients with previously untreated multiple myeloma were randomized to receive oral melphalan (0.15 mg/kg/day for seven days, followed by 0.05 mg/kg/day after recovery from the nadir of the leukocytes), BCNU (150 mg/m2 intravenously every six weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six-week course of prednisone starting at 0.8 mg/kg for the first two weeks. At week 22, one-half of the patients were randomized to receive vincristine (1 mg/m2) and prednisone (0.6 mg/kg for seven days) every two months in addition to previous therapy. The melphalan treated patients showed a significantly higher overall objective response frequency (59%), according to Myeloma Task Force criteria, when compared to those treated with BCNU (40%) or CCNU (42%). The survivals for all patients were not statistically different for the three treatment programs. However, the good-risk patients treated with melphalan had significantly longer survival (P = 0.02) than the equivalent patients who received BCNU or CCNU. The addition of vincristine and prednisone at week 2 did not significantly increase the percentage of subsequent objective responses or prolong the subsequent survival of any treatment group. It is concluded that oral melphalan is superior to BCNU and CCNU in producing objective responses and in prolonging survival in good risk patients.

Antineoplastic Agents↗
PubMed1982

Management of leukaemia-associated disseminated intravascular coagulation (DIC).

Seven patients presenting with DIC in association with acute promyelocytic and myelomonocytic leukaemia were treated with intensive chemotherapy (IC), intensive platelet support (IPS) and continuous heparinization (CH), or IC + CH but minimal platelet support (MPS), or no chemotherapy, no heparin or MPS. All four patients who received IC + IPS + CH achieved remission (survival time: 516, 400+, 371 and 368 days). The remaining three patients died early (survival time: 11, 7 and 3 days). The results suggest that a combination of IC + IPS + CH is essential in the management of leukaemia-related DIC.

Adolescent↗
PubMed1981

The superiority of CCNU in the treatment of advanced Hodgkin's disease: Cancer and Leukemia Group B Study.

In a randomized study, the effect of single agent therapy, with CCNU was compared with that of BCNU in previously treated patients with advanced Hodgkin's disease. The dosage of CCNU was 100 mg/m2 p.o. q. 6 weeks and of BCNU, 200 mg/m2, p. 6 weeks with dose modification adjusted to individual tolerance. For 60 evaluable patients the response rate (complete and partial was 60 for CCNU and 28% for BCNU (p = 0.025); median duration of response was 4.5 months and 2.0 months, respectively (P = 0.26). Median survival for responders was 11.0 months and for non-responders 5.0 months. No major difference was observed in hematologic toxicity between the two compounds. Used as single agents in equitoxic dosages, CCNU is superior to BCNU for the treatment of previously treated advanced Hodgkin's disease, and CCNU has the additional advantage of oral administration.

Adult↗
PubMed1981

MER immunotherapy and combination chemotherapy for advanced, recurrent Hodgkin's disease. Cancer and Leukemia Group B study.

The effects of chemotherapy and chemoimmunotherapy in previously treated advanced Hodgkin's disease were evaluated in a randomized study of 167 patients by CALGB. Combination chemotherapy consisted of treatment with one of three regimens with further randomization of MER (methanol extraction residue BCG) immunotherapy or no MER during chemotherapy. CVPP (CCNU, vinblastine, procarbazine, prednisone) was compared to a new combination, BAVS (bleomycin, Adriamycin, vincristine, streptozotocin), and to a third regimen consisting of alternating cycles of CVPP and BAVS. At the current analysis there is no significant difference in complete responses among the chemotherapy regimens. MER did not improve complete response frequency and was associated with significantly poorer survival for patients previously treated with chemotherapy. There was also no benefit with MER for patients with at least one pretreatment positive skin test. Because of the documented lack of therapeutic benefit and the morbidity of painful ulcers, MER treatment has been discontinued.

Adult↗
PubMed1980

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease.

Five hundred and sixty-six patients with either Stage III or IV Hodgkin's disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbazine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

Adult↗
PubMed1980

Clinical trial of VP 16--213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B.

The epipodophyllotoxin derivative VP 16--213 (NSC 141540) was studied by the Cancer and Leukemia Group B in a broad phase II trial at three dose levels: 60 mg/m2, 90 mg/m2, and 135 mg/m2 I.V. twice weekly. No correlation between dose of VP 16--213 and response frequency in a particular disease category could be demonstrated. Of the 382 patients, 8% obtained a complete (CR) or partial remission (PR), 8% showed improvement, and 14% had stable disease. By tumor type the best responses were obtained in lymphomas (8/31 CR + PR), uterus (2/9), prostate (1/5), rhabdomyosarcoma (2/6), neuroblastoma (2/4), colon/rectum (5/81), other gastrointestinal (4/32). In lung tumors, 4/80 patients obtained CR or PR. VP 16--213 has definite antineoplastic activity but the response frequency with the twice weekly schedule may be lower than that reported with other schedules.

Adult↗
PubMed1980

Central nervous system involvement at presentation in acute granulocytic leukemia. A prospective cytocentrifuge study.

We have undertaken a perspective study of the prevelance of the central nervous disease in acute granulocytic leukemia (AGL). Thirty-nine newly diagnosed patients with AGL underwent cytocentrifuge examination of cerebral spinal fluid. Seven of the 39 patients had blast cells in their cerebral spinal fluid. All seven of these patients had acute myelomonocytic leukemia (AMML). No patients with other variants of AGL demonstrated blast cells in their cerebral spinal fluid. Other high risk factors associated with meningeal infiltration were elevated serum lysozyme levels, high peripheral white blood cell count, low age, splemomegaly and the presence of infiltration in other organs. The admission rates for patients with meningeal leukemia were lower and the survival time was shorter than in both the 32 noninvolved patients and the noninvolved patients with AMML. We believe that a lumbar puncture is indicated in all patients with newly diagnosed AMML.

Adolescent↗
PubMed1980

Association of monocytic leukemia in patients with extreme leukocytosis.

Fifteen of 73 newly diagnosed patients with acute myeloid leukemia (AML), admitted to Mount Sinai Hospital between July 1977 and October 1979, presented with leukocyte counts greater than 100,000/microliter. Eleven of these 15 patients with hyperleukocytosis had myelomonocytic (AMML-M4) or monocytic (AMOL-M5) leukemia compared to 15 of 58 patients with lower white cell counts (p < 0.001). Identification of type of leukemia, using the FAB classification, was based on morphology and special stains, including myeloperoxidase, Sudan black B, periodic acid-Schiff and nonspecific esterase with and without inhibition by fluoride. The proportion of patients with splenomegaly is higher in those with hyperleukocytosis (73 percent) than in those with lower white blood cell counts (p < 0.001) regardless of cell type. Leukemic infiltration of the skin, gums and central nervous system was seen exclusively in patients with AMML and AMOL. The serum lysozyme levels were significantly higher for all patients with AMML and AMOL regardless of the white blood cell count. The mean serum lysozyme for M-4, M-5 patients was 59.7 microgram/ml compared to 18.9 microgram/ml in patients with other cell types (p < 0.0001). Patients with a white blood cell count less than or equal to 100,000/microliter had a complete remission rate of 69 percent compared to 47 percent for patients with higher white blood cell counts.

Humans↗