Biomedical subjects

F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 163 records · Page 9Linked to original sources

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

Chromosome 17 numerical abnormalities in 55 patients with non-Hodgkin's lymphoma: a fluorescence in situ hybridization study.

Monosomy 17 and structural abnormalities of the short arm of chromosome 17 have been reported to influence prognosis and treatment outcome in patients with non-Hodgkin's lymphoma (NHL). In diffuse large cell lymphoma, these abnormalities were associated with refractoriness to chemotherapy, higher proliferative rate and poor prognosis. We studied the incidence of chromosome 17 abnormalities in 55 patients with NHL by using fluorescence in situ hybridization with a directly conjugated centromeric probe for chromosome 17. Twenty-three patients (42%) were previously untreated. Thirty-four patients (62%) had diffuse large cell lymphoma, 18 (33%) had follicular low-grade lymphoma, one had small lymphocytic lymphoma, one had diffuse mixed cell lymphoma, and one had mantle cell lymphoma. Cells from benign lymphoid hyperplasia were used as controls. Eight patients (15%) had trisomy 17 in 1.2-40.7% of cells and one patient (1.8%) had monosomy 17 in 68.8% of cells. We conclude that monosomy 17 is not common in NHL. Chromosome 17 deletions should be investigated with region-specific probes to determine their clinical relevance in NHL.

Adolescent↗

PubMed1994

Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma.

OBJECTIVE: To determine the following: a reference range for serum calcitriol during hypercalcemia in a control group of patients with myeloma in whom calcitriol production is known to be appropriately suppressed; the incidence of elevated serum calcitriol levels in hypercalcemic patients with non-Hodgkin lymphoma according to this derived reference range; and the incidence of abnormal calcium metabolism in normocalcemic patients with non-Hodgkin lymphoma. DESIGN: Prospective clinical study. SETTING: Referral cancer center. PATIENTS: 2 groups of hypercalcemic patients: 16 control patients with myeloma and 22 patients with non-Hodgkin lymphoma divided into those with elevated or normal serum calcitriol levels; 1 group of 22 normocalcemic patients with non-Hodgkin lymphoma. MEASUREMENTS: Serum chemistries and intact parathyroid hormone, calcitriol, parathyroid hormone-related protein, and urinary electrolyte levels. RESULTS: On the basis of the mean serum calcitriol level of the control group plus 3 standard deviations, the reference range for serum calcitriol during hypercalcemia was defined as less than 42 pg/mL. Although serum calcium and parathyroid hormone levels in the study patients were similar to those in controls, 12 of the 22 hypercalcemic patients with non-Hodgkin lymphoma (55%) had serum calcitriol levels greater than 42 pg/mL (range, 51 to 170 pg/mL). No features distinguished the patients with elevated serum calcitriol levels from those with normal levels. Seventy-one percent of normocalcemic patients with non-Hodgkin lymphoma were hypercalciuric, and 18% had serum calcitriol levels greater than the normocalcemic reference range (20 to 76 pg/mL). CONCLUSIONS: Serum calcitriol levels are elevated in most hypercalcemic patients with non-Hodgkin lymphoma in the absence of elevated serum levels of parathyroid hormone, which implicates extrarenal calcitriol production in the pathogenesis of this syndrome. Abnormal calcium metabolism, hypercalciuria, and dysregulated calcitriol production are also common in normocalcemic patients with non-Hodgkin lymphoma.

Adult↗

PubMed1994

Polysomy of chromosome 12 in 60 patients with non-Hodgkin's lymphoma assessed by fluorescence in situ hybridization: differences between follicular and diffuse large cell lymphoma.

Sixty consecutive evaluable specimens from patients with non-Hodgkin's lymphoma (NHL) were studied for the incidence of polysomy of chromosome 12 by fluorescence in situ hybridization (FISH) with probes for the repetitive DNA sequence in the centromeric region of chromosome 12. Thirty-six samples were from follicular lymphomas (FLs), and twenty-four were from diffuse large cell lymphomas (DLCLs). Fifty-two specimens (86%) were obtained by fine-needle aspiration of a diseased node, seven (11.6%) were from involved bone marrows, and one specimen was from a pleural effusion. Twelve of the thirty-six (33%) cases with FL had trisomy 12 in 3-41% of the cells (median, 10%) (normal controls had three signals in 1.4 +/- 0.7% of cells). Trisomy 12 was found in 62% of the patients who had had FL for more than 5 years. Nine of the twenty-four cases (37%) with DLCL had more than two copies of chromosome 12 in 4-92% of the cells (median, 78%), and all nine cases were of B-cell phenotype. Unlike FL cells, some DLCL cells had 4-6 copies of chromosome 12. In previously untreated patients, 54% of DLCLs and 26% of FLs had subpopulations of cells containing more than two copies of chromosome 12 (P = 0.04). Only 2/7 cases of DLCL with polysomy 12 had rearrangement of the BCL2 gene, indicating that the majority of DLCL cases with polysomy 12 did not result from histologic transformation of low grade follicular lymphomas. These data demonstrate that FISH of interphase cells is a sensitive method for detecting numerical abnormalities of chromosome 12 in NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗

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

High incidence of monosomy 18 in lymphoid malignancies that have bone marrow and peripheral blood involvement.

We studied the incidence of numerical chromosome 18 abnormalities in 107 patients with lymphoid malignancies by fluorescence in situ hybridization (FISH) using a directly conjugated centromeric probe for chromosome 18. Samples were obtained by fine needle aspiration of diseased nodes, bone marrows or peripheral blood. Monosomy 18 was more common in chronic lymphocytic leukemia (43%), small lymphocytic lymphoma (28%), and follicular lymphomas (12.5%) than in diffuse lymphomas (5.3%; p < 0.01). Monosomy 18 was detected in 9.7-17.1% of the cells in non-Hodgkin's lymphoma (NHL) (background, 5.4%; 99% CI, 4.2%-6.6%) and in 8%-16.7% (median, 10%) of the cells in (CLL) (background, 3.4%; 99% CI, 2.5%-4.3%). All patients with monosomy 18 were found to have bone marrow involvement. Of all untreated patients who had disease involving the bone marrow, 32% were found to have monosomy 18. Trisomy 18 was detected in 3.6%-48.2% of the cells in NHL (background, 0.9%; 99% CI, 0.2%-1.6%) and was most common in diffuse large-cell lymphoma (34%) and follicular lymphomas (31%). None of the patients with small lymphocytic lymphoma or chronic lymphocytic leukemia had trisomy 18. There was no correlation between trisomy 18 and response to treatment or clinical presentation. In this study, monosomy 18 was observed frequently in patients with lymphoid malignancies that involve the bone marrow and peripheral blood. Our data suggest that important gene(s) located on chromosome 18 may be involved in homing of the malignant lymphocytes to the bone marrow and peripheral blood.

Adult↗

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↗

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

Growth inhibition of follicular small-cleaved-cell lymphoma cells in short-term culture by interleukin-3.

BACKGROUND: The role of interleukin-3 (IL-3) in stimulating the growth of early myeloid progenitor cells is very well established. Therefore, IL-3 has been incorporated into many post-bone-marrow transplantation and intensive chemotherapy programs for the treatment of solid tumors and hematologic malignancies, including lymphomas. However, the effect of IL-3 on normal and malignant lymphocytes has not been well studied. PURPOSE: The purpose of this study was to evaluate the in vitro effect of IL-3 on the growth of follicular small-cleaved-cell lymphoma (FSCCL). MATERIALS AND METHODS: IL-3 receptor expression on the surface of CD19+ cells was determined by two-color flow cytometry measuring the receptor-binding of biotinylated IL-3 to CD19+ B-cells. Seven cases of FSCCL were compared to six normal controls. Cell proliferation was evaluated by [3H]thymidine incorporation into cells grown in suspension cultures. RESULTS: All seven cases of FSCCL expressed the IL-3 receptor on the surface of CD19+ cells, whereas all six cases of CD19+ cells isolated from the peripheral blood of normal donors did not express IL-3 receptors. IL-3 had antiproliferative activity against FSCCL as manifested by a decrease in [3H]thymidine incorporation and a decrease in the total number of cells after 72 hours of culture. CONCLUSION: IL-3 inhibits the growth of FSCCL cells in vitro. Clinical trials to evaluate the in vivo effect of IL-3 in patients with FSCCL are warranted.

Antigens, CD↗

PubMed1994

Long-term prognostic importance of primary Ki-1 (CD30) antigen expression and anaplastic morphology in adult patients with diffuse large-cell lymphoma.

BACKGROUND: We retrospectively assessed the long-term prognostic importance of primary CD30 antigen expression and of anaplastic large-cell morphology (ALCL) in adult patients with previously untreated diffuse large-cell lymphoma (DLCL), including cases of immunoblastic lymphoma, and identified their clinical features. MATERIALS AND METHODS: We examined available archival paraffin-embedded or frozen pathologic material and medical records of adult patients with previously untreated DLCL seen at M.D. Anderson Cancer Center (MDACC) between January 1978 and May 1989. RESULTS: Sixty-seven cases of DLCL and seven cases of IBL (a total of seventy-four heretofore referred to as DLCL) were identified. Twenty-two of the 74 patients were positive for the CD 30 antigen. For these 22 patients the rates of complete remission, survival, and time to treatment failure (TTF) were 86%, 82%, and 77%, respectively, at 81 months. When compared with the group of 54 patients which stained negative for CD 30, the long term survival of CD 30-positive DLCL was favorable (82% vs. 49%, p = 0.08). ALCL morphology was present in two-thirds of the patients with CD 30-positive DLCL but did not affect survival and TTF rates. Among patients with CD 30-positive DLCL, 16 patients without skin involvement were younger and had a low failure rate (13%) compared with six patients with skin involvement who were older and had a high failure rate (50%); however, the latter group had a more indolent course after failure and thus both groups had similar survival rates. CONCLUSIONS: Primary CD 30 positivity is associated with a favorable long-term prognosis in adult patients with DLCL treated with doxorubicin-containing chemotherapy. ALCL morphology among these patients does not affect the outcome. Patients with CD30-positive DLCL and skin involvement have a higher failure rate than those without skin involvement, but similar overall survival.

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

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.

PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.

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

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↗