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Biomedical subjects

P McLaughlin

Publications and source records attributed to P McLaughlin.

At least 109 records · Page 6Linked to original sources
PubMed1994

The gallium scan predicts relapse in patients with Hodgkin's disease treated with combined modality therapy.

The gallium scan (GS) is an important indicator of disease activity in untreated Hodgkin's disease, especially in the upper torso, and may be an important predictor of results for patients who have completed chemotherapy and radiotherapy (XRT). To better define the importance of the GS in predicting treatment results in a group of patients treated with uniform therapy, we performed GS prior to treatment in 46 patients with pathologically or clinically staged I-III Hodgkin's disease who received three cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) followed by XRT. Staging methods included computerized tomography (CT) of the chest, abdomen, and pelvis, lymphangiogram, and the GS, using 8 to 10 millicuries with single photon emission computed tomography (SPECT) of the upper and lower torso. Only 3 patients had negative GS before chemotherapy. After three cycles of NOVP and prior to XRT, the other 43 had repeat GS performed. Complete remission (CR) was judged by disappearance of disease after all therapy without considering GS results. The CR for those with initial positive GS was 93%. The three-year freedom from progression result for stage I-II was 94%, and the three-year overall survival was 96%; corresponding results for stage III were 86% and 100%, respectively. None of the prognostic factors for analysis, including bulky adenopathy, hilar involvement, or B symptoms, was an important predictor of results. However, only 1 of the 33 with a negative GS after these NOVP has had progressive disease compared to 3 of the 10 with a GS that remained positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: high remission rates and reversion to negative of peripheral blood bcl-2 rearrangement.

BACKGROUND: Advanced-stage low-grade lymphoma is characterized by initial responsiveness to many conventional therapies but ultimate relapse. Intensive therapy approaches with non-cross-resistant regimens have not been extensively explored. The polymerase chain reaction (PCR) can be used to monitor for the presence of cells with rearrangement of bcl-2, and provides a sensitive and stringent parameter of disease activity and treatment response that may have clinical utility. PATIENTS AND METHODS: From 1988 to 1992, 138 evaluable patients were treated with 3 sequential chemotherapy regimens, as well as with interferon alfa 2b (IFN) in combination with corticosteroids. Nineteen patients had serial PCR monitoring for bcl-2 rearrangement. RESULTS: Among a subset of 58 patients who had an initial phase of IFN plus prednisone, the response rate was 59%, mostly partial remissions (PR). With the chemotherapy program, 65% have achieved complete remission to date, and 30% PR. By PCR analysis, 13 of 19 tested achieved negative status ('molecular remission'), a much higher frequency of molecular remission than has been seen with standard therapies, and these molecular remissions appear to correlate with a lower likelihood of relapse. CONCLUSIONS: Intensive conventional-dose chemotherapy can achieve high rates of remission, even when monitored by the stringent PCR technique.

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

Hodgkin's disease with a mediastinal mass greater than 10 cm: results of four different treatment approaches.

BACKGROUND: Management of Hodgkin's disease (HD) and large mediastinal adenopathy (LMA) usually includes intensive chemotherapy (CT) with or without radiation therapy (XT) regardless of stage. PATIENTS AND METHODS: One hundred and eighteen evaluable patients received one of four treatment regimens: (1) 6 cycles of MOPP or similar CT and XT; (2) 2 of MOPP followed by XT; (3) 6 of CVPP/ABDIC (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, decarbazine, prednisone, lomustine) followed by XT; or (4) 3 of NOVP (mitoxantrone, vincristine, vinblastine, procarbazine) and XT. XT doses included 30-40 Gy to areas of nodal involvement noted prior to therapy. RESULTS: Complete remission (CR) rates for groups 1, 2, 3, and 4 were 100%, 85%, 87%, and 96%. Respective 3-year freedom from progression (FFP) results were 88%, 66%, 82%, and 88%, and 3-year freedom from tumor mortality (FTM) results were 100%, 84%, 84%, and 100%. The presence of B symptoms and stage IV disease was correlated with lower CR and 3-year FFP rates but similar 3-year survival. CONCLUSIONS: Results of this study suggest that patients with stage I-III Hodgkin's disease and LMA greater than 10 cm treated with 3 NOVP and XT have results similar to those obtained for a similar group of patients treated with 2 to 6 MOPP or 6 CVPP/ABDIC and XT. NOVP has also been reported to produce limited toxicity in this trial and should be considered as an alternative to MOPP or doxorubicin-containing regimens in treatment of patients with early-staged disease and LMA greater than 10 cm.

Adolescent↗
PubMed1994

Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low beta 2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase.

BACKGROUND: Primary mediastinal large cell lymphoma (PMLCL) is an emerging entity. New parameters can help define it. MATERIALS AND METHODS: Retrospective analysis of medical records from 35 patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1990. Immunohistochemical evaluation of tissue specimens. Determination of survival (S) and time to treatment failure (TTF). RESULTS: The median age was 34 years and 69% were females. Eight-three percent presented with symptoms of mediastinal involvement. While 100% of the patients presented with bulky mediastinal disease and 72% had elevated pretreatment serum lactate dehydrogenase, only 6% presented with an elevated pretreatment serum beta 2 microglobulin. The lymphoma cells lacked CD21 staining. For the 18 patients treated initially at M.D. Anderson Cancer Center, S and TTF curves rates after doxorubicin-based regimens (plus radiotherapy in 14 cases) were 72% and 61%, respectively, at 5 years follow-up (median, 42 months). Four out of six patients who received autologous bone marrow transplant as salvage therapy are currently alive without disease at follow-up times of 21, 25, 32, and 54 months. CONCLUSION: Primary mediastinal large cell lymphoma has characteristic clinicopathological features to which another can be added, that of an inverted pattern of bulky disease, high LDH and low beta 2 M in serum. The response to therapy is comparable to that of intermediate-grade lymphomas, although the numbers in the study are small. Our preliminary data suggest a possible role for autologous bone marrow transplantation (ABMT) as salvage therapy.

Adult↗
PubMed1994

Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.

PURPOSE: Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination. PATIENTS AND METHODS: Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function. RESULTS: The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months). CONCLUSION: FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗
PubMed1994

Asthma requiring mechanical ventilation. A low morbidity approach.

STUDY OBJECTIVE: There is considerable uncertainty about the clinical features, respiratory physiology, and optimal management of patients with asthma requiring mechanical ventilation. Furthermore, the ventilatory and pharmacologic management of asthma requiring mechanical ventilation remain controversial. We hypothesized (1) that there are clinically identifiable and pathophysiologically different subgroups presenting with asthma requiring ventilation; (2) that lower dose steroid therapy (< 400 mg/d intravenous hydrocortisone) is adequate; (3) that permissive hypercapnia is safe; (4) that prolonged paralysis is generally unnecessary; and (5) that clinical outcome would be favorable in patients treated with this approach. DESIGN: Review of medical records and intensive care charts and statistical analysis of findings. SETTING: ICU of tertiary institution. PATIENTS: Thirty-five consecutive cases of life-threatening asthma requiring mechanic ventilation. RESULTS: Three clinical subgroups of ventilation-requiring asthmatics could be identified. Those presenting with steady deterioration (10), those with unstable asthma followed by a sudden "dip" (16), and those with a sudden unexpected dip (9). Patients in the first group had a significantly lower PaCO2 (p < 0.01) at presentation, but required ventilation for longer periods. Those in the second group had a significantly higher PaCO2 (p < 0.01) and required ventilation for a shorter period. Those in the third group had an intermediate PaCO2 level before intubation and the shortest period (p < 0.01) of mechanical ventilation. Five patients experienced their sudden dip after ingesting aspirin. Ten cases received "high" dose hydrocortisone therapy (mean: 980 mg/24 h), and 25 received lower dose hydrocortisone (mean: 341 mg/24 h). No differences in illness severity at presentation or outcome could be detected between these two groups. Mean duration of ventilatory support was 36 h and mean duration of the ICU stay 52.1 h. Muscle relaxation was used in 12 patients for a mean period of 11.1 h. One patient was brain dead on arrival. All others survived. CONCLUSIONS: Life threatening asthma is an endpoint for several different clinical patterns of disease. No major clinical advantage could be found in our group of patients when high-dose steroids were used. Long-term use of muscle relaxants and prolonged mechanic ventilation are rarely needed in the management of patients with life-threatening asthma and excellent results can be achieved with a relatively simple management strategy.

Adult↗
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↗
PubMed1993

Variant plasma gelsolin responsible for familial amyloidosis (Finnish type) has defective actin severing activity.

Familial amyloidosis, Finnish type is caused by a single base mutation in gelsolin, an actin filament severing and capping protein that is present in most tissues and in blood plasma. The mutation replaces aspartic acid with asparagine at residue 187 of the plasma sequence. This renders the gelsolin susceptible to proteolysis as a consequence of which amyloid protein is formed. Here it is shown that the mutant protein in plasma from a patient homozygous for this mutation lacks both actin severing and nucleating activities. Evidence is presented that the cleaved mutant gelsolin has dissociated under non-denaturing conditions and that the resultant 65,000 and 55,000 M(r) C-terminal fragments aggregate.

Actins↗
PubMed1993

Trypanosoma cruzi trypanothione reductase. Crystallization, unit cell dimensions and structure solution.

We have reproducibly crystallized recombinant trypanothione reductase from Trypanosoma cruzi. Yellow tetragonal crystals in the shape of elongated prisms have unit cell dimensions of a = 92.8 A, c = 156.6 A, Laue symmetry of 4/m and are suitable for a detailed structural analysis. Diffraction data to 2.7 A resolution have been recorded using synchrotron radiation at the Daresbury laboratory. The structure has been solved by molecular replacement calculations using this synchrotron data and our previously determined Crithidia fasciculata enzyme structure as a search model. The space group has been identified as P4(3) with a homodimer of approximate molecular mass of 108 kDa in the asymmetric unit. Diffraction beyond 2.5 A has been recorded when large freshly grown crystals are exposed to X-rays. Refinement of the structure is in progress.

Animals↗
PubMed1993

Hodgkin's disease: study of treatment intensities and incidences of second malignancies.

BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non-Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non-Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage.

Actuarial Analysis↗
PubMed1993

CHOP-Bleo plus interferon for stage IV low-grade lymphoma.

BACKGROUND: Alpha interferon (IFN) is an effective single agent for patients with low-grade lymphoma, but until 1982 had not been integrated with standard chemotherapy for these patients. Since relapse from complete remission (CR) is the rule for patients with advanced stage low-grade lymphoma, a maintenance IFN schedule was explored for patients in CR. PATIENTS AND METHODS: From 1982-1987, 127 patients with stage IV low-grade lymphoma were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) for 9-18 mo. (median 13 mo.), followed by interferon alfa-n-1 (Wellferon) maintenance therapy for 24 mo. for CRs. RESULTS: The overall response rate for the entire treatment program was 73% CR and 23% partial remission. The median follow up was 59 months. At 5 years, survival was 74%, failure-free survival (FFS) 47%, and FFS of CRs 60%. Compared to a group of 96 patients with similar pretreatment clinical features treated with CHOP-Bleo from 1972-1982, this represents a significant improvement for both overall FFS (p = 0.01) and FFS of CRs (P < 0.01). Toxicity from the IFN maintenance was generally acceptable, but even at the modest dose employed in this trial (3 x 10(6) U/m2 three times weekly), dose modification was required in more than 30% of patients, usually because of fatigue. CONCLUSIONS: The integration of IFN and conventional chemotherapy is feasible and effective. Maintenance IFN prolongs remission duration for patients with stage IV low-grade lymphoma.

Adult↗
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

Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin's lymphomas.

PURPOSE: Treatment of lymphomas with combination chemotherapy with or without radiation therapy (XRT) can result in long-term or permanent azoospermia. PATIENTS AND METHODS: Semen analyses of lymphoma patients were performed before, during, and after treatment with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy. Some of the patients also received other drugs or radiation therapy. RESULTS: Although no patients were azoospermic before treatment, all were rendered azoospermic during treatment. Following the completion of treatment, the fraction of patients whose sperm counts recovered increased gradually over 5 years and plateaued by 7 years, with two thirds of the men achieving normospermic levels. Scattered gonadal radiation dose and cumulative cyclophosphamide dose were found to be independently significant determinants of recovery: the fraction of patients whose sperm counts recovered to 10 x 10(6)/mL were 83%, 47%, and 20% for those who received less than 9.5 g/m2 of cyclophosphamide, greater than 9.5 g/m2 of cyclophosphamide, and pelvic XRT, respectively. The inclusion of additional drugs and interferon alfa did not significantly affect the long-term recovery of spermatogenesis. CONCLUSION: Pelvic XRT and cumulative cyclophosphamide dosages greater than 9.5 g/m2 are associated with a high risk of permanent sterility in lymphoma patients treated with the CHOP-Bleo regimen.

Adolescent↗
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↗