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Biomedical subjects

L E Robertson

Publications and source records attributed to L E Robertson.

At least 37 records · Page 2Linked to original sources
PubMed1995

High molecular weight DNA fragmentation: a critical event in nucleoside analogue-induced apoptosis in leukemia cells.

Cleavage of DNA into internucleosomal fragments is one of the characteristics of apoptosis. However, searches for in vivo evidence of nucleosomal DNA fragmentation in leukemia cells freshly obtained from patients during chemotherapy frequently failed to reveal nucleosomal multimers (DNA ladders). It is not clear whether this type of DNA cleavage is an essential event in drug-induced apoptosis and thus a denominator of cell killing, or whether the internucleosomal DNA fragments are merely the by-products of the apoptotic process. Here, we report our investigation into the role of DNA fragmentation in apoptotic cell death induced by anticancer nucleoside analogues, both in cell culture and in leukemia patients undergoing chemotherapy. Using a 5'-end DNA-labeling technique and pulsed field gel electrophoresis, we detected fragmentation of DNA in two distinct size classes, internucleosomal and high molecular weight (predominantly 50 kb) DNA fragments, in a human leukemia cell line exposed to the nucleoside analogues fludarabine and gemcitabine. We further demonstrated that the two types of DNA fragmentation were separate events, distinguishable by their requirements for Ca2+ and responses to phorbol ester treatment. The drug-treated cells underwent morphological changes of apoptosis even after internucleosomal DNA fragmentation was selectively inhibited by intracellular Ca2+ chelation, or by treatment with phorbol ester. In contrast, neither apoptotic morphology nor internucleosomal DNA fragmentation was observed when the high molecular weight DNA fragmentation was blocked by inhibition of nucleoside analogue incorporation into DNA. These results suggest that cleavage of DNA into large fragments may be an initial event that is critical for drug-induced apoptosis, whereas activation of a Ca2+-dependent endonuclease to cleave DNA at internucleosomal sites is not an absolute requirement for the execution of the apoptotic cell death program. Further studies of leukemic lymphocytes obtained from 9 patients with chronic lymphocytic leukemia during therapy with fludarabine revealed high molecular weight DNA fragmentation, which was correlated with a decrease of peripheral lymphocytes in 6 patients, whereas only 1 of the 15 patients evaluated for nucleosomal DNA fragments showed the DNA ladders. These results indicate that high molecular weight DNA fragmentation occurs in vivo, and may be correlated with the cytotoxic action of the anticancer drugs. Further study of the association of high molecular weight DNA fragmentation with clinical response to chemotherapy is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

Adult↗
PubMed1994

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone.

Adolescent↗
PubMed1994

Combination of fludarabine and arabinosylcytosine for treatment of chronic lymphocytic leukemia: clinical efficacy and modulation of arabinosylcytosine pharmacology.

Previous studies have demonstrated that treatment with fludarabine 4 h prior to arabinosylcytosine (ara-C) potentiates the accumulation of the active triphosphate of ara-C (ara-CTP) in leukemic lymphocytes. The clinical efficacy of this combination was evaluated in 15 patients with chronic lymphocytic leukemia (CLL) that was advanced in their disease (median Rai stage, IV) and refractory to treatment with fludarabine. Patients received 0.5 g/m2 ara-C infused i.v. over 2 h followed at 20 h by a 30-min infusion of 30 mg/m2 fludarabine. At 24 h, an identical dose of ara-C was infused. To intensity the therapy and to determine the duration of fludarabine potentiation of ara-CTP accumulation, six additional patients with Rai stage III or IV CLL were treated with an amended 2-week protocol. On week 1, 30 mg/m2 fludarabine was infused over 30 min, followed 4 h later by a 2-h infusion of 0.5 g/m2 ara-C; on week 2, the fludarabine dose was followed 4 h later by a 4-h infusion of ara-C (1.0 g/m2). In all, 1 partial remission and 7 minor responses in 1 or more disease sites were observed in the 21 patients. The major treatment-related toxic effects were myelosuppression and infection. Comparison of the ara-CTP accumulation area under the concentration-time curve (AUC) in circulating CLL cells of patients on the amended protocol demonstrated a significant (P = 0.001) 1.6-fold (range, 1.4- to 2.0-fold) increase after fludarabine administration. Although the initial rates of ara-CTP accumulation were similar for the 2-h and 4-h infusions, ara-CTP accumulation continued for up to 4 h in four of five patients who received the longer infusion. The activity of the fludarabine and ara-C combination is being evaluated in in vitro model systems and in phase II clinical trials in combination with other drugs.

Adult↗
PubMed1994

The role of fludarabine in hematological malignancies.

Fludarabine monophosphate, a synthetic nucleoside analog, has been shown to have considerable activity in a number of lymphoid malignancies. In chronic lymphocytic leukemia the response rates can exceed 70% with a considerable proportion of complete remissions being attained. These rates are markedly superior to earlier therapies with which complete remission was uncommon. It also has significant activity in previously treated patients for whom effective salvage regimens were unsatisfactory. In addition, fludarabine shows substantial activity in low grade non-Hodgkin's lymphoma, both as initial treatment and as salvage therapy. Fludarabine is effective in Waldenstrom's macroglobulinemia and is active in other low grade lymphoid malignancies. Major toxicities are reversible myelosuppression and depletion of T lymphocytes. The use of fludarabine in hematological malignancies will be reviewed, with reference to its mode of action and future use in combination therapies.

Adult↗
PubMed1994

Fludarabine--present status and future developments in chronic lymphocytic leukemia and lymphoma.

BACKGROUND: Fludarabine monophosphate (fludarabine) is an adenine nucleoside analogue active in indolent lymphoproliferative diseases which has an increasing role in studies incorporating combinations of agents which exploit biochemical modulation, inhibition of DNA repair, and radiosensitizing effects. PATIENTS AND METHODS: Patients with lymphoma and chronic lymphocytic leukemia (CLL) treated at the M. D. Anderson Cancer Center (MDACC) and reports in the literature form the basis of this report. RESULTS: CLL has traditionally been treated with alkylating agents and corticosteroids. In this study, fludarabine has shown marked cytoreductive ability in both previously treated patients and untreated patients. In the former group, there has been a 55% response rate in 374 patients, and 79% in the untreated CLL group. Fludarabine has also been very active in the management of low-grade lymphomas, with two-thirds of patients with follicular lymphoma and half of those with other indolent lymphomas responding. Waldenstrom's macroglobulinemia is also sensitive to the effects of fludarabine. Combination regimens were developed incorporating the substantial effectiveness of fludarabine and mitoxantrone where in the previously treated low-grade lymphoma group 25 of 28 patients (89%) responded. Fludarabine has the effect of increasing the triphosphate form of cytosine arabinoside in acute and chronic leukemic cells. This modulation has now been translated into therapy for acute leukemia and combined with cisplatinum in refractory CLL. Fludarabine inhibits DNA repair and enhances cross-linking of DNA by cisplatinum. The combination of fludarabine, ara-C, and cis-platinum is now being used in refractory CLL. Fludarabine is a radiation sensitizer, inhibiting repair of DNA damage. Studies are ongoing with this combination. CONCLUSIONS: Fludarabine is a potent molecule with a wide range of biochemical effects. Optimal use of this drug alone and in combination is continuing to be explored.

Adrenal Cortex Hormones↗
PubMed1994

Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). PATIENTS AND METHODS: A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved. Results were compared with those in 85 newly diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF. RESULTS: Patients in both groups were relatively old (median age of all patients, 63 years), and were likely to have prognostically unfavorable cytogenetic abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF accelerated recovery to > or = 1,000 neutrophils (P < .0001; median, 34 days for FA, 21 days for FLAG), but logistic regression provided no evidence that the CR rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63% and 53%, respectively. This may reflect relatively high rates of death before neutrophil recovery in both groups. Rates of infection were similar in both groups. The follow-up duration in remission is short, and much of these data remain censored. To date, survival is similar with FA and FLAG. CONCLUSION: On average, G-CSF before, during, and after FA had no effect on CR or infection rates in this population, in which elderly patients and poor prognostic factors were prevalent. The use of FA and laminar airflow rooms rather than more usual therapy needs to be considered when analyzing the results.

Aged↗
PubMed1994

Clinical experience with fludarabine in leukaemia.

Fludarabine (Fludara) is a new purine analogue that was first entered into clinical trials in 1982. Results of initial studies with high dosages (> 96 mg/m2/day for 5 to 7 days) of fludarabine in acute leukaemia showed significant cytoreductive activity but a high incidence of severe irreversible neurotoxicity. The results of subsequent studies with lower dosages of 25 to 30 mg/m2/day for 5 days in chronic lymphocytic leukaemia (CLL) and low grade lymphomas have shown this regimen to be effective and safe, with almost no significant neurotoxicity. At present, the major role of fludarabine in leukaemia is in the management of CLL. In previously treated patients with CLL, responses are obtained in more than 50% of patients, with two-thirds of those responses being complete remissions according to the National Cancer Institute Working Group (NCIWG) criteria for complete response and partial response. The major causes of morbidity associated with fludarabine in CLL are infections and febrile episodes. These occur more frequently in previously treated patients and those with advanced stage of disease. Myelosuppression is dose limiting and a small proportion of patients with CLL develop moderate to severe and sometimes protracted myelosuppression. Administration of combined fludarabine and cytarabine (cytosine arabinoside; ara-C) alone (FA regimen) or together with granulocyte colony-stimulating factor (FLAG regimen) produced high response rates in previously treated refractory patients with acute leukaemia and previously untreated patients with acute myelogenous leukaemia or myelodysplastic syndrome. The wide range of biochemical and biological activities of fludarabine suggests that it will have an expanding role in future combinations in the treatment of both acute and chronic leukaemias.

Antineoplastic Agents↗
PubMed1994

The expanding role of fludarabine in hematologic malignancies.

The major clinical experience with fludarabine has been obtained in patients with chronic lymphocytic leukemia (CLL). In the initial studies in previously treated patients with CLL, the complete and partial response rate (CR + PR) was over 50%, and in previously untreated patients with CLL, a CR + PR rate of 75-80% was noted with or without the addition of prednisone. Subsequent clinical trials have also demonstrated major activity with fludarabine in Waldenstrom's macroglobulinemia. Fludarabine was noted to be an active agent in indolent lymphoma in phase I/II studies. Approximately 60% of patients with follicular lymphoma respond to fludarabine when it is administered as a single agent. Many of these remissions are complete remissions despite patients having received extensive prior therapy. Combination programs are being developed for application in CLL and indolent lymphoma. Because of the activity of fludarabine in inhibiting DNA repair, it has been combined with cisplatinum and cytosine arabinoside and plans are in place to explore the radiation sensitizing effect of fludarabine in clinical trials. A combination of fludarabine plus ara-C is now being used in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) and a combination of fludarabine, ara-C, and G-CSF (FLAG) has been combined with idarubicin for the management of these conditions. Many of these activities of fludarabine are associated with its interaction with many enzymes which are important in DNA and RNA metabolism and in DNA repair. It is anticipated that these actions will be explored in a wider range of studies subsequently.

Antineoplastic Agents↗
PubMed1994

Therapy-related leukemia and myelodysplastic syndrome in chronic lymphocytic leukemia.

A retrospective analysis was performed to determine the incidence and clinical features of acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) developing in chronic lymphocytic leukemia (CLL) patients. AML/MDS occurred in 3/1374 CLL patients seen at a single institution between 1972 and 1992. The median follow-up exceeded 7 years and 72% of these patients had received prior alkylating agent therapy. The expected number of AML/MDS developing in a general population of the same size was 1.2 as calculated from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program data (observed-to-expected ratio = 2.49; 95% confidence interval = 0.9-7.3; p = 0.12). Although, not included in the incidence calculation, four patients with CLL were referred at the time of development of AML/MDS. CLL and AML/MDS were diagnosed concurrently in two patients. Three of the patients had received no prior alkylating agents. The median survival was 17 months in patients who had received no prior treatment, and 5 months in those who had received prior chemotherapy. Our results suggest that patients with CLL in whom AML/MDS develops have similar prognoses to other patients with AML/MDS. Furthermore, this analysis does not provide evidence for a heightened risk of AML/MDS in CLL patients, despite treatment with known leukemogenic agents.

Aged↗
PubMed1993

Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment.

Two hundred sixty-four patients with chronic lymphocytic leukemia were treated with fludarabine 30 mg/m2 intravenously for 30 minutes each day for 5 days and with prednisone 30 mg/m2 orally each day for 5 days. Courses were repeated monthly. Of the 264 patients. 125 patients (47%) had Rai stage III-IV disease; 169 patients (64%) were previously treated with a median of 3 prior regimens; and 138 of them (82%) were refractory to therapy with alkylating agents. The overall response (OR) and complete response (CR) rates in the 169 previously-treated patients were 52% and 37%; these were 74% and 63%, respectively, in Rai stage O-II patients and declined to 64% and 46%, respectively, in Rai III-IV disease. Among the previously untreated patients, the OR and CR rates were 79% and 63%, these being 85% and 70%, respectively, in Rai O-II patients, and declining to 64% and 46%, respectively, in Rai III-IV disease. The incidence of minor infections or fever of unknown origin was similar in all patient groups and occurred in 22% of courses. The incidence of sepsis and/or pneumonia was significantly correlated with the extent of prior therapy and with Rai stage, and ranged from 3% of courses in the previously untreated Rai O-II patients, to 13% of courses in the previously treated Rai III-IV patients. Listeria sepsis or Pneumocystis carinii pneumonia was noted in 14 patients. With therapy, CD4 levels were uniformly depressed from a median 1,015/microL pretreatment to a median 159/microL after 3 months of fludarabine therapy. Median time to progression in previously treated patients was 22 months. In previously untreated patients, median time to progression was 30 months for patients who achieved a partial remission and has not been reached in patients who achieved a CR with a median follow-up of 2 years. The median survival was 18 months for previously treated patients and has not been reached for previously untreated patients. Response rates in previously treated and untreated patients, as well as infection rates, were identical to those seen in 110 patients treated with the same dose schedule of fludarabine alone. Logistic regression analysis selected 4 factors to be significantly associated with worse response: Rai III-IV stage disease, prior therapy, older age, and low albumin levels. The regression equation was used to derive a probability of response based on the 4 characteristics. When the model was applied to the same population, patients could be divided into 4 prognostic groups with different outcomes.

Antigens, CD↗
PubMed1993

Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2'-deoxyadenosine and 9-beta-D-arabinosyl-2-fluoroadenine.

2-Chloro-2'-deoxyadenosine (CldAdo) and 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A) have shown marked activity in the treatment of indolent lymphoid malignancies. Based on the susceptibility of various lymphocyte populations to apoptosis, we investigated whether CldAdo or F-ara-A would induce this process in lymphocytes from patients with chronic lymphocytic leukemia (CLL). In vitro exposure of leukemic lymphocytes to CldAdo or F-ara-A for 24 to 72 hours elicited features of apoptosis visible by light and electron microscopy. Analysis of DNA integrity showed DNA cleavage into nucleosomal-sized multimers. Using a quantitative assay, drug-induced DNA fragmentation was both time and dose dependent. Inhibition of active macromolecular synthesis did not prevent drug-induced fragmentation; however, both drug-induced and spontaneous DNA fragmentation were prevented by intracellular calcium chelation. In vitro culture with phorbol ester generally decreased drug-induced DNA cleavage. After prolonged incubation, CLL cells exhibited spontaneous cleavage; albeit, at significantly lower rates than drug-treated cells. Heterogeneity was observed for spontaneous and drug-induced DNA fragmentation and was significantly lower in B-leukemic cells obtained from patients with high-risk and refractory disease. We conclude that CldAdo and F-ara-A are potent inducers of apoptotic death in CLL and that this feature correlates with the disease status.

Adenosine Triphosphate↗
PubMed1993

Richter's syndrome: a report on 39 patients.

PURPOSE: The incidence, clinical features, laboratory findings, and treatment results of 39 patients with Richter's syndrome (RS) are reported. PATIENTS AND METHODS: Thirty-nine of 1,374 patients with chronic lymphocytic leukemia (CLL) developed RS. RESULTS: Features associated with RS included systemic symptoms (59%), progressive lymphadenopathy (64%), extranodal involvement (41%), elevation of lactate dehydrogenase (LDH; 82%), and a monoclonal gammopathy (44%). Analysis of the CLL karyotype showed no specific chromosomal abnormality that conferred increased risk; however, multiple abnormalities were common. Patients at all Rai stages and in complete response (CR) were at risk, including three CR patients with no residual disease at the level of detection by dual-parameter flow cytometry or restriction analysis for immunoglobulin (Ig) gene rearrangements. The incidence was not higher in patients who had received prior fludarabine or chlorodeoxyadenosine. The median survival duration was only 5 months, despite multiagent therapy. Patients who responded had prolonged survival durations (P < .001). Three of eight patients who survived more than 1 year had a de novo presentation of both CLL and large-cell lymphoma (LCL). Comparison of surface light-chain analysis from both low- and high-grade components demonstrated isotypic light-chain expression in 12 of 15 patients. Ig heavy- and light-chain gene rearrangement analysis showed identical rearrangement patterns in five of five patients. CONCLUSION: The clinical, laboratory, and survival characteristics of our RS patients were similar to those reported in earlier studies. Ig gene rearrangement and light-chain isotype analysis support a common origin for CLL and LCL. Despite progress in the treatment of CLL, the development of LCL remains a serious complication and continued surveillance in all CLL patients is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

High-dose cytosine arabinoside in chronic lymphocytic leukemia: a clinical and pharmacologic analysis.

Twenty-seven patients with B-cell chronic lymphocytic leukemia (CLL) or a related lymphoid malignancy were treated with high-dose cytosine arabinoside (ara-C) at a dosage of 3 gm/m2 administered over 2 hours every 12 hours at one to four doses per course, which were repeated at 4-week intervals. Median patient age was 60 years. Fifty-four percent of CLL patients had Rai stage III or IV disease and the median number of prior therapies was three. Two patients achieved a complete response, five had a partial response, and two had clinical improvement for an overall response rate of 33%. The median duration of response was 9 months. Myelosuppression and infection were the main toxicities. Intracellular levels of the active metabolite ara-C triphosphate varied among patients, but comparisons of pharmacokinetic parameters revealed no significant differences between responders and non-responders. We conclude that high-dose ara-C has modest activity in CLL and that its use in combination with other agents in the treatment of CLL is warranted.

Aged↗
PubMed1993

New initiatives with fludarabine monophosphate in hematologic malignancies.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a-week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/microL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (> 30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimetabolites, Antineoplastic↗