Is further intensification of treatment warranted in acute nonlymphoblastic leukemia?
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Mertelsmann.
Explore the source record for details and available documents.
A Burkitt's-like B-cell lymphoma (BLL) has recently been shown to be associated with the acquired immunodeficiency syndrome (AIDS), which affects homosexual men. We report cytogenetic studies of two BLL tumors in homosexual men. Both tumors had chromosome translocations characteristic of Burkitt's lymphoma (BL), one the t(8;14) and the other the t(8;22). The pathway of lymphomagenesis in this disorder is discussed in the light of recent data on chromosome change and localization of immunoglobulin genes and oncogenes.
Seventy-nine adult patients with acute nonlymphoblastic leukemia (ANLL) were treated on the L-6 protocol at Memorial Sloan-Kettering Cancer Center between May 1970 and January 1974. Forty-two patients achieved a complete remission (CR) and nine of these are still disease free, with a minimum of seven years of follow-up. An extensive statistical analysis has been carried out on a large number of pretreatment and treatment characteristics to identify factors related to CR and remission duration. Multivariate regression techniques yielded as favorable characteristics associated with CR, in order of importance: young age at diagnosis, the presence of Auer rods at diagnosis, and treatment with Pseudomonas vaccine. A regression model for remission duration identified as favorable prognostic factors for long-term remission: at most two courses of induction therapy, an intermediate age range, and a low platelet count at diagnosis.
Interleukin 2 (IL-2), produced with and without co-stimulation by the Burkitt's lymphoma line Daudi, was purified 37,000-fold to apparent homogeneity from lymphocyte conditioned medium by (NH4)2SO4 precipitation, DEAE-cellulose ion-exchange chromatography, gel filtration, and chromatography on blue agarose and on Procion-red agarose. The purified IL-2 showed a 10(6) U/mg protein sp act. IL-2 produced in the absence of Daudi cells had a mol wt of 26,000 as measured by gel filtration and an isoelectric point of 6.7. This IL-2 showed a 16,000 and 17,000 mol wt in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). IL-2, produced in the presence of Daudi cells (10(6)/ml), showed a mol wt of approximately 14,000, as measured by both gel filtration and SDS-PAGE, and an isoelectric point of 8.1. The purified IL-2 lacked detectable interferon (alpha and gamma), granulocyte-macrophage colony-stimulating factor, B cell growth factor, T cell-replacing factor, and thymocyte-differentiating activity and was free of any contaminating proteins as judged by silver staining in SDS-PAGE. All three molecular forms of IL-2 were biologically active at concentrations of 10(-11) - 10(-10) M, supporting the growth of human and murine cytotoxic T cell lines.
A 38-year-old male with terminal transferase positive acute lymphoblastic leukemia experienced fever, polymicrobial bacteremia, gastrointestinal bleeding, abdominal pain during induction therapy, and remission. Cecal perforation, Aspergillus peritonitis, and subsequent disseminated aspergillosis were successfully managed with colon resection, drainage, and antibiotic and antifungal therapy. Serologic tests for antibody to Aspergillus were repeatedly negative.
Explore the source record for details and available documents.
Twenty-four adults with ALL were treated with AMSA alone or in combination. Twenty-two were treated at time of relapse and two patients after failing primary induction therapy. All had been treated with anthracyclines prior to receiving AMSA. Of the 22 patients with ALL in relapse, 4 achieved a complete remission. Two of these patients have relapsed while receiving maintenance chemotherapy; one died 1 mo after achieving remission due to the occurrence of cholycystitis in the setting of pancytopenia and one patient underwent bone marrow transplantation and is in remission at 8 mo after the second remission. Both patients who failed primary induction therapy remain in remission at 11 and 36 mo, respectively. The use of AMSA should be considered for patients with ALL who fail primary induction as well as those whose leukemia becomes resistant to conventional agents.
Explore the source record for details and available documents.
Fifty-one adult patients with acute nonlymphocytic leukemia (excluding acute promyelocytic leukemia) were treated on the L-12 protocol. The L-12 differed from the preceding L-6 in that 2,2-anhydro-1-B-D-arabinofuranosyl-5-fluorocytosine (AAFC), replaced arabinosylcytosine (ara-C) together with 6-thioguanine (TG) for remission induction. Achievement of remission was followed by an extended 14-week multi-drug consolidation program. With this more intense regimen, an overall complete remission rate of 49% and a median remission duration of 23.7 months were achieved; these results were not significantly better than the 57% complete remission rate and 8.6 months median remission duration obtained with the L-6 regimen. Four year disease-free survival was 22% on the L-12 compared with 16% on the L-6 protocol. No relationship between prognosis and FAB classification was found on either the L-6 or the L-12 protocol.
A case of disseminated infection with Trichosporon cutaneum, a fungus that causes white piedra, is described. The patient, a 58-year-old barber with acute leukemia, had fever, myalgias and skin lesions. He was receiving cytotoxic drug therapy and prednisone, was severely neutropenic and was being treated with broad spectrum antibiotics. Blood cultures and a biopsy of the skin lesion grew T. cutaneum. He died despite amphotericin B therapy. At autopsy, widespread infection with T. cutaneum was present. T. cutaneum is another fungus capable of causing widespread systemic disease in the immunocompromised host.
Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase which is only found in immature cells of lymphoid lineage (pre-T/pre-B). Because of this restricted distribution of TdT, biochemical and immunofluorescence techniques have been employed to determine the distribution of TdT phenotypes in human leukemias and lymphomas, showing high levels of TdT in approximately 95% of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), approximately 50% of patients with acute undifferentiated leukemia (AUL), approximately 10 of patients with acute nonlymphoblastic leukemia (ANLL), and approximately 30% of patients with chronic myeloid leukemia (CML) and other myeloproliferative (MPS) or myelodysplastic (MDS) syndromes in blast crisis. High levels of TdT activity are associated with a clinical response to remission inducing therapy with vincristine and prednisone in a high proportion of patients (50%-90%), irrespective of clinical and morphologic diagnosis. Preliminary studies furthermore suggest that TdT might serve as a sensitive indicator of subclinical disease in ALL in complete remission.
Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.
Lymphocytes of lymphocyte-rich pleural effusions and venous blood from 16 cancer patients, 7 patients with benign pleural effusions and blood from 23 normal blood donors, were examined for cytological features, rosette-forming capacity, immunofluorescent staining, and PHA-stimulated DNA synthesis. Total protein and immunoglobulin levels were also determined. Metastatic effusions revealed approximately 40% higher content of immunoglobulins G, A and M (P less than 0.002) as well as of total protein (P less than 0.005) than non-metastatic pleural effusions. However, the serum of the non-cancer patients contained approximately 50% higher level of Ig than in cancer patients (P less than 0.001). Whilst there was no significant difference in the relative T- or B-cell contents of pleural effusions between cancer and non-cancer patients (P greater than 0.05) spontaneous proliferation of lymphocytes was significantly increased (P greater than 0.01), which led to a lower PHA-stimulated transformation index in pleural effusions from cancer patients than in all other lymphocyte sources examined (P less than 0.001).
Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.
One-hundred-one adult patients with ALL were analyzed to determine the prognostic implications of splenomegaly occurring at any time during the course of their illness. The clinical status of the spleen at presentation was not found to be of major prognostic significance. Complete response rates, remission durations, and survivals did not differ between patients with and without splenomegaly at presentation. An enlarged spleen accompanied relapse in four patients. In six additional patients, splenomegaly was present during complete remission, and splenectomies performed in five of these patients revealed no evidence of leukemia to account for the splenomegaly. Splenectomy does not appear to be detrimental, as all five patients are currently in complete remission from 20 to 63 mo after splenectomy. Evidence implicating the spleen as a source of an antibody directed against autologous leukemia cells in one patient is reviewed.
Marrow culture studies revealed a spectrum of qualitative and quantitative defects in granulocyte-macrophage progenitors (GM-CFC) of patients with chronic myeloid leukemia in chronic phase and blastic crisis. Parallel culture studies and terminal transferase determinations revealed that a significant proportion of patients in blastic crisis possess two coexisting acute phase clones, one lymphoblastic and one myeloblastic. Measurement of response to and production of T cell growth factor showed that the leukemic blast cells from patients with TdT-positive blastic crisis produced the factor, but did not exhibit a proliferative response to exogenous factor. This phenotype was identical to that observed in TdT-positive acute lymphoblastic leukemia. Additional regulatory defects were identified in CML, since leukemic GM-CFC proliferation was resistant to inhibition by concentrations of prostaglandin E, which are markedly inhibitory for normal GM-CFC. The self-renewal or recloning capacity of GM-CFC was also identified as a unique feature of some patients with CML. The addition of retinoic acid to primary cultures of leukemic GM-CFC completely abolished this recloning capacity.
A simplified system for classification of aggregate incidence and growth pattern in the CFU-c (colony-forming units in culture) assay, allowing simple and reproducible interpretation of test results, was developed and applied to 552 bone marrow samples from 202 patients with acute leukemia. Ninety-six consecutive patients with acute nonlymphoblastic leukemia were studied at diagnosis. The microcluster growth pattern ("acute myeloid leukemia-type") found in 57% of the patients was significantly associated with higher remission induction rates on both protocols (p = 0.004). No relationship between growth pattern at diagnosis and remission duration was observed. The acute myeloid leukemia-type growth pattern was found to be more frequent in leukemias exhibiting morphological evidence for partial myeloid or monocytic differentiation. The favorable prognostic significance of Auer rods previously described was recognized in two CFU-c growth pattern categories. Of patients exhibiting an acute myeloid leukemia-growth pattern and Auer rods, 89% obtained complete remissions compared to 38% in the Auer rod-negative group showing other growth pattern variants. The CFU-c assays performed during complete remission on 354 samples of 48 patients with acute nonlymphoblastic leukemia and, as a control, on 85 samples of 43 patients with acute lymphoblastic leukemia revealed marked spontaneous as well as chemotherapy-related fluctuations of aggregate incidence and growth pattern. These and similar observations obtained with other assay systems are probably of major pathophysiological significance but preclude clinical application of the CFU-c assay to the monitoring of remission status in patients with acute nonlymphoblastic leukemia.
Explore the source record for details and available documents.