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Biomedical subjects

P McLaughlin

Publications and source records attributed to P McLaughlin.

At least 91 records · Page 5Linked to original sources
PubMed1996

High rate of prolonged remissions following combined modality therapy for patients with localized low-grade lymphoma.

PURPOSE: Involved field (IF) radiation can cure as many as 40% to 50% of patients with stage I-II low-grade lymphoma. We sought to improve these results by prospectively evaluating the combination of IF radiation and chemotherapy consisting of 10 courses of cyclophosphamide, vincristine, prednisone, and bleomycin, with doxorubicin added in a risk-adapted manner (COP/CHOP-Bleo). PATIENTS AND METHODS: From 1984 until December 1992, 91 patients, median age 56 years (range 28 to 77 years), with clinical stage I-II low-grade lymphoma were treated. No patients were excluded on the basis of age or organ function. RESULTS: A complete response was attained in 99% of evaluable patients. Treatment-related toxicity was mild, and no deaths occurred during therapy. With a median follow-up of 60 months, there have been only 16 relapses. The actuarial freedom from relapse rate at five years is 82% (95% confidence interval 71% to 89%) and at 10 years is 73%. At five years the overall survival rate is 90% (95% confidence interval 81% to 95%) and at ten years it is 82%. Of the clinical features examined, only older age (> 56 years; p = 0.07) was associated with shorter survival. No features examined were predictive of disease relapse. CONCLUSION: The combination of IF radiation and risk-adapted COP/CHOP-Bleo chemotherapy is well-tolerated, produces a very high rate of complete remission, and with a median follow-up of five years, has produced lower rates of relapse and better overall survival than has been reported for IF radiation alone in patients with clinically-staged I-II low-grade lymphoma.

Adult↗
PubMed1996

Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma.

PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro by inhibiting P-gp function. Therefore, we determined whether addition of cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed NHL were eligible if they had no intervening treatment after failure to respond to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal, and hepatic function, no serious cardiac disease, no CNS involvement, and no antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six hours after the beginning of cyclosporin A, the immediately preceding paclitaxel dose was administered over 3 hours. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two cycles, and those patients who achieved at least a partial response received a maximum of six courses. RESULTS: All 26 patients entered were assessable for toxicity and 25 were assessable for response. One patient whose disease had progressed during paclitaxel treatment had a partial remission after the addition of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease progressed in 17 patients (71%) and did not respond in seven (25%). Serum cyclosporin A A levels measured at the time of initiation of paclitaxel infusion were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient with preexisting asthma had an acute bronchospasm during the first cycle and was removed from the study. There were no renal or hepatic toxicity and no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule did not reverse established clinical resistance to paclitaxel, which suggests that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel resistance in this patient population.

Adult↗
PubMed1996

No effect of 96-hour paclitaxel infusion in patients with relapsed non-Hodgkin's lymphoma refractory to a 3-hour infusion schedule.

PURPOSE: Preclinical data suggest that the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is schedule-dependent. Schedule dependency is currently under investigation in ongoing randomized trials. PATIENTS AND METHODS: Twelve patients with relapsed non-Hodgkin's lymphoma (NHL) refractory to a 3-hour infusion of 200 mg/m2 Taxol were crossed over to receive a 96-hour infusion of 140 mg/m2 Taxol every 3 weeks in an outpatient setting. Premedication with corticosteroids and antihistamines was not used. Patients who did not achieve at least a partial remission (PR) after two courses or whose disease progressed after one course were removed from the study. RESULTS: All 12 patients were assessable for response. Eleven patients received at least two courses and one patient received one course of 96-hour Taxol infusion. None of the 12 patients crossed over to receive 96-hour Taxol infusion achieved a PR or complete response (CR). Eight patients (67%) developed progressive lymphoma, three (25%) had stable disease, and only one (8%) had a minor response. No major hypersensitivity reactions or life-threatening toxicities were observed. CONCLUSION: Ninety-six-hour Taxol infusion does not produce significant responses in patients with NHL refractory to 3-hour Taxol infusion. Until the results of an ongoing multicenter trial comparing a 3- with a 96-hour infusion are published, the use of 96-hour Taxol infusion in NHL patients should be restricted to investigational programs. Because 48- to 72-hour infusions can produce higher plasma concentrations of Taxol than a 96-hour infusion, these schedules should be investigated to determine if they can induce better clinical responses.

Adult↗
PubMed1996

Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma.

PURPOSE: Although most patients with indolent lymphomas respond to initial therapy, virtually all experience relapse. Secondary therapy is often beneficial, but responses are rarely, if ever, durable. We conducted this phase II trail to evaluate the therapeutic efficacy and toxicity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma. PATIENTS AND METHODS: Fifty-one patients with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m2/d intravenously (IV) on days 1 to 3, mitoxantrone 10 mg/m2 IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimethoprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis carinii (PCP) prophylaxis. RESULTS: Responses were complete (CR) in 24 patients (47%) and partial (PR) in 24 (47%). The median failure-free survival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with high serum lactate dehydrogenase (LDH) or beta2-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effects were modest. Infections occurred in 12% of courses. Almost half of the infections were proven or suspected opportunistic infections, including six cases of dermatomal herpes zoster and two cases of proven PCP pneumonia. CONCLUSION: The FND combination is highly active in patients with recurrent or relapsed indolent lymphoma and results in a high percentage of CRs. Because of the risk of opportunistic infections, we currently recommend prophylaxis with TMP-SMX and advise deletion of corticosteroids for patients who develop opportunistic infections.

Aged↗
PubMed1996

Clinical experience with fludarabine in hemato-oncology.

Fludarabine monophosphate (Fludara) is a purine analogue which entered clinical trials in 1982. Although inactive in solid tumors, Fludara has marked activity in indolent lymphoproliferative disorders. The exact mechanism of action of Fludara is uncertain. Fludara has been established as the most active single agent in chronic lymphocytic leukemia (CLL) in single arm and comparative clinical trials. The activity has been demonstrated in both previously treated and initially treated patients. Marked activity has been noted in patients with low grade lymphoma, in particular, those with a follicular morphology and in Waldenstrom's macroglobulinemia. Combinations of fludarabine with alkylating agents, anthracyclines, and anthraquinones have led to clinically useful combination approaches. The ability of fludarabine to modulate the levels of the triphosphate form of cytosine arabinoside (ara-C) in acute leukemia cells has led to the development of combinations of fludarabine and ara-C. These combinations have demonstrated marked activity in treatment of relapsed and previously untreated patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The ability to modulate the activity of pyrimidines and to inhibit repair of DNA damage caused by alkylating agents, anthracyclines, and other DNA active drugs suggest that the future of fludarabine will be in combination approaches to modulate the activity of other agents. These activities may extend its role to use in solid tumors.

Antineoplastic Agents↗
PubMed1995

Transformation of chronic lymphocytic leukemia to lymphoma of true histiocytic type.

BACKGROUND: Chronic lymphocytic leukemia (CLL) may evolve into large cell lymphoma (Richter's syndrome), prolymphocytic leukemia, acute lymphoblastic leukemia, and myeloma. METHODS: A patient with CLL that transformed into a lymphoma of true histiocytic type is described, and the literature on the association of these two disorders is reviewed. RESULTS: Lymphomas of true histiocytic type developing as an aggressive terminal phase of CLL previously have been reported in nine patients. Fever and rapidly increasing lymphadenopathy and splenomegaly were the most common signs and symptoms. As with de novo lymphoma of true histiocytic type, extranodal involvement of the soft tissue, gastrointestinal tract, kidneys, bone marrow, liver, and lungs was documented among the 10 patients with lymphoma of true histiocytic type transformed from CLL. The median interval between diagnosis of CLL and the evolution to lymphoma of true histiocytic type was 25.5 months. Patients with lymphomas of true histiocytic type after CLL were treated with fludarabine and various other combination chemotherapy regimens with only short-lived responses. The median time to death after transformation was only 33 days (range, 10 days to 5 months). CONCLUSION: Lymphomas of true histiocytic type appear to represent an additional, though uncommon, form of transformation in CLL. Although their presentation is reminiscent of other intermediate to high grade lymphomas, they can be distinguished based on their morphologic and immunophenotypic features. In the patients described in this study to date, transformation of CLL to lymphomas of true histiocytic type is a poor prognostic sign, with survival generally of only days to weeks.

Bone Marrow↗
PubMed1995

Identification of the trapped calcium in the gelsolin segment 1-actin complex: implications for the role of calcium in the control of gelsolin activity.

The X-ray structure of the complex of actin with gelsolin segment 1 revealed the presence of two calcium ions, one bound at an intramolecular site within segment 1 and the other bridging the segment directly to actin. Although earlier calcium binding studies at pH 8.0 revealed only a single calcium trapped in the complex (and also in the binary gelsolin-actin complex), it is here shown that two calcium ions are bound under the conditions of crystallization at physiological pH. Mutation of acidic residues in either actin or segment 1 involved in ligation of the intermolecular calcium ion resulted in loss of one of the bound calcium ions at pH < 7, but not at pH 8. Thus the calcium ion trapped in the segment 1-actin complex is that located at the intramolecular site. The implications of this for gelsolin function are discussed.

Actins↗
PubMed1995

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation.

PURPOSE: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of refractory non-Hodgkin's lymphoma: a phase II study.

In an attempt to circumvent clinical multidrug resistance, we conducted a Phase II trial of cyclosporin plus combination chemotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been previously treated with a doxorubicin-containing regimen, received doxorubicin 50 mg/m2 intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2 mg i.v. (day 1), and etoposide 75 mg/m2 i.v. daily for 4 days (days 1-4). Four days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88 mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for 9 days). Cyclosporin dose escalation was permitted, conventionally defined therapeutic levels of cyclosporin were achieved; this drug was well tolerated at these doses. The study was closed due to a poor response rate; only one patient achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities included gastrointestinal haemorrhage (one patient), sensory neuropathy (two patients), stomatitis (two patients), and transaminase elevation (one patient). Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels) occurred in 33% of patients. There were no treatment associated deaths. Prolonged neutropenia and thrombocytopenia were the primary haematological toxicities. Although the addition of cyclosporin at this dose and schedule did not improve response rates in this patient group, future trials using higher doses of cyclosporin with combination chemotherapy may warrant further investigation.

Adult↗
PubMed1995

A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas.

BACKGROUND: We have previously reported that combination chemotherapy based on the drugs cytarabine/platinum is effective in recurring lymphomas. In this phase II study, we prospectively studied a combination regimen of mesna/ifosfamide, mitoxantrone and etoposide (MINE) in patients with recurring lymphoma who had already received cytarabine/platinum but did not respond to the treatment. PATIENTS AND METHODS: 48 patients received MINE at the following doses: mesna 1.33 g/m2 i.v. daily x 3, and 500 mg p.o. daily 4 hours after each i.v. dose; ifosfamide 1.33 g/m2 i.v. daily, given concurrently with mesna, x 3 d; mitoxantrone 8 mg/m2 i.v. on day 1; and etoposide 65 mg/m2 i.v. daily x 3. Treatment cycles were 21-28 days apart, depending on patients' blood counts, with a maximum number of 6 cycles in responding patients. The histologic grade of the lymphomas according to the Working Formulation was low in 8 patients and intermediate in 40 patients. In the latter group, 12 were transformed from low grade. RESULTS: Overall, 48% of the patients responded, with 21% having a complete response (CR), and 27% having a partial response (PR). The median survival time was 9 months, and the median follow-up of survivors is 51 months at this writing. Median time to treatment failure was 12 months for patients with complete responses, and 5 months for patients with partial responses. The most serious complication was myelosuppression, with 2 deaths resulting from neutropenic infection. CONCLUSION: The MINE regimen induced responses in a moderate fraction of patients after their prior exposure to cytarabine/platinum salvage therapy, indicating there is no absolute cross resistance between these drug regimens.

Adult↗
PubMed1995

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma.

PURPOSE: Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied. PATIENTS AND METHODS: Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses. RESULTS: Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate-grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity. CONCLUSION: At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL.

Adult↗
PubMed1995

Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP.

PURPOSE: We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs. PATIENTS AND METHODS: Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients. RESULTS: The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M < 3 mg/dL and LDH normal), 61%; intermediate (beta 2M > or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M > or = 3 mg/dL and LDH above normal), 0%. CONCLUSION: MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study.

Adult↗
PubMed1995

Rising serum lactate dehydrogenase often caused by granulocyte-or Granulocyte-macrophage colony stimulating factor and not tumor progression in patients with lymphoma or myeloma.

Since rising serum lactate dehydrogenase (LDH) heralds progression in patients with lymphoma or myeloma we investigated the significance of its elevations during chemotherapy supported by granulocyte (G-) or Granulocyte-Macrophage (GM-) colony stimulating factors (CSF). To Exclude effects of resistant disease we analyzed 52 courses of therapy in 36 responding patients. During hematologic recovery LDH increased above normal in 53% and 85% of patients with leukocyte counts of 10,000/microL and 15,000/microL, respectively. After CSF discontinuation LDH fell to or towards normal during 20 courses with adequate follow-up. Therefore rising serum LDH in patients with lymphoma or myeloma may be caused the CSF administration during chemotherapy and not by progressive disease. Proper identification of this effect can prevent unnecessary tests or treatment delays.

Adult↗
PubMed1995

Risk classification for large cell lymphoma using lactate dehydrogenase, beta-2 microglobulin, and thymidine kinase.

We have previously proposed a staging system for large cell lymphoma using the two serum markers beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH). We recently tested this model in a different cohort of patients with large cell lymphoma and also examined the possible contribution of thymidine kinase (TK), a previously reported serologic prognostic factor. Using an inclusion criteria in the multivariate analysis for both forward and backward selection of p < 0.15, only LDH, B2M, and TK were significant independent prognostic factors for both time to treatment failure (TTF) and survival. Inclusion of TK in the serologic model resulted in three significantly different risk groups for both TTF and survival. Corresponding endpoints at three years were: 1) good risk (no markers elevated, n = 43): 78%, 91%; 2) intermediate risk (1 or 2 markers elevated, n = 47): 41%, 36%; 3) poor risk (3 markers elevated, n = 11): 0%, 0%. This analysis extends the observation of the independent prognostic significance of B2M and LDH. The addition of TK permits a more precise estimate of risk, contributing to the utility of a serological staging system for large cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin- vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate-etoposide-dexamethasone. Application of prognostic models to data analysis.

BACKGROUND: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs. METHODS: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index. RESULTS: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis. CONCLUSIONS: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.

Adolescent↗
PubMed1994

A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide, methylprednisolone, high-dose arabinoside, and cisplatin as salvage therapy for relapsing and/or refractory lymphomas.

PURPOSE: To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) as consolidation therapy after complete or partial responses (CR or PR, respectively) or after crossover therapy for progressive disease. METHODS: Patients received MINE(o) consisting of mesna, 1.33 g/m2 infused over 1 hour daily x 3 followed 4 hours later by oral mesna at 500 mg; ifosfamide, 1.33 g/m2 infused over 1 hour daily x 3; mitoxantrone, 8 mg/m2 intravenously on day 1, and oral VP-16, 30 mg/m2 daily x 13. The ESHAP regimen consisted of intravenous VP-16, 40 mg/m2 infused over 2 hours daily x 4; methylprednisolone, 500 mg intravenously daily x 4; cytosine arabinoside, 1.5 g/m2 infused over 3 hours on day 4; and cisplatin, 25 mg/m2 given as a continuous 24-hour infusion daily x 4. Statistical analysis was performed using the 2-stage design described by Simon. For the oral VP-16 regimen to be of interest, at least 36% patients had to achieve a complete remission. RESULTS: The overall response rate achieved with MINE(o) was 40% (15% CR, 25% PR). Seven patients with prior exposure to cytosine arabinoside and cisplatin (AP) received MINE(o) alone of whom only one achieved a response (CR). Thirteen patients without prior exposure to AP received consolidation (2 patients) or crossover (11 patients) therapy with ESHAP. Crossover therapy with ESHAP further improved the response in only two of five patients with partial response to MINE(o) and none of six patients who failed MINE(o). Median response duration for the patients who received MINE(o)/ESHAP was 12 weeks (range, 4-55 weeks). CONCLUSIONS: Oral VP-16 combined with ifosfamide/mesna and mitoxantrone at the doses and schedules indicated has little activity against relapsed and/or refractory lymphomas. Crossover therapy with ESHAP did not further improve the response rate. The duration of response after MINE(o)/ESHAP was short.

Adolescent↗
PubMed1994

Stage, serum LDH, and performance status predict disease progression and survival in HIV-associated lymphomas.

PURPOSE: This is a review of treatment of 44 patients with positive HIV serology (positive HIV) and lymphoma. MATERIALS AND METHODS: Twenty patients had diffuse large-cell lymphoma (DLCL), and 18 had small noncleaved-cell lymphoma (SNCCL). Three had Hodgkin's disease (HD) and 3 had diffuse small- or mixed-cell lymphoma. These patients received intensive chemotherapy regimens for management of their disease; most were regimens in use at our institution for patients with lymphoma who did not have positive HIV. RESULTS: The complete response to treatment (CR) was 77% for all patient, 80% for those with DLCL, and 72% for those with SNCCL. Stage, serum LDH, and performance status were predictors of complete remission and freedom from progression. Though there was a tendency for patients with a T4-cell count of < or = 200 to have a higher risk of opportunistic infections while receiving therapy, most infections were controllable with appropriate antibiotic management. More than one-half of the deaths in this study occurred after completion of therapy in complete remission, with a median survival of only 11 months, and were attributable to AIDS-related complications. CONCLUSIONS: Our data suggest that (1) patients with lymphoma who have positive HIV have responses to chemotherapy similar to those expected for patients who are HIV-negative; (2) most infectious complications are manageable with appropriate therapy during treatment; and (3) after completion of chemotherapy, treatment should focus on control of progression of AIDS-related complications.

AIDS-Related Opportunistic Infections↗