Biomedical subjects

F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 235 records · Page 13Linked to original sources

PubMed1988

Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin's disease.

From 1981 to 1983, 208 patients with recurrent or refractory lymphoma were treated with methylglyoxal-bis-guanylhydrazone (methyl-GAG), ifosfamide, methotrexate, etoposide (MIME). The complete remission (CR) rate was 24% and CR plus partial remission (PR) was 60%. Response was higher for aggressive than for indolent cell types. Median duration of CRs was 16.5 months and median survival of all patients was 9 months. In view of the in vitro synergism between cisplatin and high-dose cytarabine, we recently designed the DHAP regimen, which consists of cisplatin, 100 mg/m2 IV over 24 hours; cytarabine, 2 g/m2 IV over two hours every 12 hours for two doses; and dexamethasone, 40 mg orally daily for 4 days. There were 28 of 90 (31%) CRs and 22 of 90 (24%) PRs. Median duration of CR is 15 months; median survival of all patients is 6 months. The major toxicities have been infection (31%) and moderate to severe renal dysfunction (20%). In contrast to MIME, response rates did not differ significantly between aggressive and indolent cell types. A high-dose regimen (CBV) consisting of cyclophosphamide, 6 g/m2; carmustine, 300 mg/m2; and etoposide, 250 mg/m2 daily for 3 days followed by autologous bone marrow transplant (ABMT) has been successfully used to treat 62 patients with Hodgkin's disease recurrent or refractory after mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (MOPP/ABVD)-like regimens. A CR rate (47%) has been observed; 83% of these CRs remain alive and free of disease with a median follow-up of 19 months. This regimen appears to have curative potential in 40% of all cases and in 60% of cases treated after the first or second relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Prognostic factors with high-dose melphalan for refractory multiple myeloma.

High doses of melphalan (HDM) and dexamethasone were administered to 43 patients with advanced multiple myeloma, 36 of whom were refractory to both standard melphalan-prednisone and vincristine-adriamycin-dexamethasone (VAD). Forty-four percent responded with greater than 75% reduction in calculated tumor mass, including three patients who achieved a complete remission. The response rate to HDM was 56% in 18 relapsing patients and 50% in 12 patients with less than 12 months of primary drug resistance, but it was only 23% among the remaining 13 unresponsive patients. A high early mortality rate of 30% was confined to 26 patients with either poor performance (Zubrod greater than 1) or impaired renal function (creatinine greater than 1.4 mg%). When this toxic treatment was given to the 21 patients with good performance (Zubrod less than 2) whose disease lacked high serum lactic dehydrogenase (less than or equal to 500 U/L) as a recently recognized feature of high-grade myeloma, a superior median survival of 18 months was obtained as opposed to only 3 months for the 22 remaining patients (P less than .001). Thus, when employed in a timely fashion, HDM overcomes resistance to standard chemotherapy and VAD and benefits selected patients with advanced myeloma.

Aged↗

PubMed1988

Bcl-1 gene rearrangements in B cell lymphoma.

We analyzed 50 B cell lymphoma samples by Southern blot analysis, using the bcl-1 and heavy chain immunoglobulin (JH) probes with two or more restriction endonucleases. All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences. The three samples showed the t(11;14)(q13;q32) chromosome translocation, and all three contained rearranged JH fragments that comigrated with the rearranged bcl-1 fragment. The breakpoint of the translocation occurred within a 1.6-kb region on chromosome 11 in the three cases. Two of the three patients had primary refractory disease. Two of the three patients had gastrointestinal involvement. Bcl-1 rearrangement may identify an unusual subset of patients with primary refractory disease with gastrointestinal involvement. It may also describe a unique subset of large cell lymphoma patients transformed from diffuse small cell histology.

B-Lymphocytes↗

PubMed1988

Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP).

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗

PubMed1987

Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification.

By means of the polymerase chain reaction (PCR) technique, DNA sequences were amplified that flank the crossover sites of a characteristic chromosomal translocation for follicular lymphomas, t(14;18)(q32;q21). This technique permitted the detection of cells carrying the t(14;18) hybrid DNA sequences at a dilution of 1:100,000. The remission marrow and blood samples of a patient with follicular lymphoma and the t(14;18) failed to show any abnormality by morphological examination and conventional Southern blot analysis. However, the t(14;18) hybrid DNA sequences were detected by the PCR technique. Thus, this technique is a highly sensitive tool to detect minimal residual cells carrying the t(14;18) and has the potential to identify a subpopulation of patients with subclinical disease.

Base Sequence↗

PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗

PubMed1987

HLA class II antigen associated invariant chain gene expression in malignant lymphoma.

Expression of the gene encoding HLA class II antigen-associated invariant chain was studied in several types of fresh human malignant lymphoma by Northern blot analysis or slot-blot analysis. The invariant chain mRNA levels decreased with the stage of B-lymphocyte differentiation to plasma cells such as in immunoblastic lymphoma (IBL) or multiple myeloma (MM). The invariant chain gene (In-gene) was expressed in diffuse large cell lymphoma (DLCL), while its expression was hardly detected in IBL. It is suggested that the difference in In-gene expression between DLCL and IBL could be useful in distinguishing these two morphologically similar diseases.

Genes, MHC Class II↗

PubMed1987

Results of MIME salvage regimen for recurrent or refractory lymphoma.

Based on encouraging results of two previous ifosfamide-VP-16 salvage combinations, methyl-gag was added to ifosfamide, methotrexate, and etoposide (VP-16). This combination is called MIME. A total of 208 patients with recurrent lymphoma were treated with this regimen. Response rates were 24% for complete remission and 36% for partial remission. The MIME regimen was more effective in patients who were treated after being off front-line therapy for longer than 6 months. However, responses were also seen in patients with disease clearly resistant to front-line therapy, suggesting that MIME was at least partially non-cross-resistant with front-line doxorubicin-containing regimens. The 15-month median relapse-free survival of complete responders and the 9-month overall median survival time for all patients treated were both similar to results from previous ifosfamide-VP-16 combination use. This regimen has been effective in the treatment of patients with recurrent or refractory lymphoma, but cannot be considered curative in the majority of cases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease.

Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse.

Adolescent↗

PubMed1987

Activity of bisantrene in refractory lymphoma.

A total of 50 evaluable adult patients with relapsing lymphoma and two with Hodgkin's disease received bisantrene by central iv catheter every 3 weeks, at doses of 350 mg/m2 for patients with adequate marrow reserve and 300 mg/m2 for those with compromised marrow reserve. The overall response rate was 30% for 50 patients with malignant lymphoma, including seven complete remissions (14%) and eight partial remissions (16%). Neither patient with Hodgkin's disease responded. The 16 patients with follicular lymphomas did particularly well, with 31% attaining complete remission and 25% attaining partial remission. Five of seven complete responders remain in remission at 16-24+ months; two have relapsed, at 13 and 20 months. Leukopenia, of brief duration, was the most common toxic effect. Fever during neutropenia occurred in 23% of courses. There was minimal cardiotoxicity with cumulative doses of up to 7080 mg/m2 of bisantrene. Bisantrene is an effective and well-tolerated agent for the treatment of malignant lymphoma.

Adult↗

PubMed1986

Stage I-II follicular lymphoma. Treatment results for 76 patients.

Clinical features and treatment results are analyzed for 76 patients with Stage I-II follicular lymphoma seen between 1974 and 1981. During this period, 66% of the patients received involved-field radiotherapy (XRT) alone, and 34% received chemotherapy with or without XRT. At 5 years, the overall survival was 67%, the cause-specific survival was 73%, and the relapse-free survival (RFS) was 48%, with no relapses to date among nine patients followed beyond 60 months. Adverse prognostic features for survival included extranodal disease and elevated serum lactate dehydrogenase. For RFS, adverse features included extranodal disease and bulky abdominal disease. The RFS was significantly better for patients receiving chemotherapy with or without XRT than for XRT alone (64% versus 37% at 5 years, P = 0.02), despite a higher frequency of adverse prognostic features in the chemotherapy-treated group. About 50% of Stage I-II follicular lymphoma patients may be curable, and the inclusion of chemotherapy in the initial treatment may increase the potentially curable fraction.

Adult↗

PubMed1986

Chromosomal abnormalities in lymphoma and their correlations with nucleic acid flow cytometry.

Cytogenetic studies were performed on 25 samples obtained from 25 patients with lymphoma. Fourteen of these were also simultaneously studied with nucleic acid flow cytometry to determine percent S-phase and DNA content (ploidy). In 17 cases (68%), evaluable metaphases were obtained. The evaluable metaphase rate was higher in previously untreated patients (15/19 or 79%). All but two cases showed abnormal karyotype. All five cases showing either the t(8;14) or t(8;22) abnormality were associated with extremely high percent S-phase values, ranging from 36% to 47%, which is in the range of high-grade lymphomas according to our previous experience. Four of these cases were diagnosed as Burkitt's lymphoma and one as diffuse large cell lymphoma. Further review of this latter case resulted in the pathologic diagnosis being changed to Burkitt's lymphoma. Three patients had either numerical or structural abnormalities of chromosome #21 [two cases of extra chromosomes and one i(21q)]. All three cases were diagnosed as diffuse large cell lymphoma. Four instances of trisomy 12 were identified. Only one of these was diagnosed as diffuse well-differentiated lymphocytic lymphoma. The remaining three were Burkitt's lymphoma in two and diffuse large cell lymphoma in one. Two instances of t(14;18) were observed. This is the characteristic abnormality of follicular lymphomas. One of these cases was a follicular large cell lymphoma. The second case had possibly originated from a follicular mixed lymphoma and had evolved into a diffuse mixed cell type. Both of these cases had low S-phase values in the range of low-grade lymphomas. The correlation between ploidy as determined by flow cytometry and cytogenetic analysis was good whenever the DNA index was elevated. However, when the DNA index was 1.0 (diploid), concordant measurements were observed in only five of eight cases. Flow cytometry detected one instance of clearly abnormal ploidy, which was thought to be diploid by cytogenetics. This case most likely represents a "false negative" cytogenetic determination.

Adolescent↗

PubMed1986

Central nervous system prophylaxis with combined intravenous and intrathecal methotrexate in diffuse lymphoma of aggressive histologic type.

With the use of a multivariate regression model, 21 patients with diffuse lymphoma were identified as having greater than 15% risk of experiencing relapse in the central nervous system (CNS). The efficacy of a combination of sequential intravenous methotrexate (MTX) (1 g/m2) and intrathecal MTX in preventing relapse in the CNS and improving survival times was assessed. A comparable historical control group of patients with similar risk of CNS relapse and who did not receive any CNS prophylaxis was used. The CNS relapse-free survival rate (RFS) was improved in patients who received CNS prophylaxis (95% versus 59% at 2 years; P = 0.01). Pretreatment serum lactic dehydrogenase (LDH) levels correlated with the incidence of relapse in the CNS in the control group (P = 0.01). In patients with high pretreatment serum LDH levels (greater than 225 U/L), CNS RFS was improved in those who received CNS prophylaxis (RFS at 2 years: 91% versus 46%; P = 0.02). Both CNS RFS (100% versus 38% at 2 years; P = 0.03) and survival rates (100% versus 38% at 2 years; P = 0.02) were improved in six patients with histologic type other than large cell. In 15 patients with large cell lymphoma, no significant differences in CNS RFS (93% versus 75% at 2 years; P = 0.29) and survival rates (43% versus 44% at 2 years; P = 0.56) were observed. Cerebrospinal fluid MTX levels were above the therapeutic level of 1 X 10(-6) M for at least 20 hours in 90% of courses of combined MTX. The MTX combination used is an effective and non-neurotoxic CNS prophylaxis method. Because the comparison between different methods of CNS prophylaxis is difficult to make without a precise idea of the expected CNS relapse rate, use of the multivariate regression technique is recommended.

Adult↗

PubMed1986

9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate pharmacokinetics in plasma and tumor cells of patients with relapsed leukemia and lymphoma.

The pharmacokinetics of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) in plasma and its biologically active 5'-triphosphate (F-ara-ATP) in leukemic cells obtained from the peripheral blood and bone marrow was evaluated in patients with hematologic malignancies subsequent to the first dose of 20-125 mg/m2 per day for 5 days of F-ara-A 5'-monophosphate (F-ara-AMP) administered as an IV bolus over 30 min. The terminal half-lives of elimination of both F-ara-A (8 h) in plasma and intracellular F-ara-ATP (15 h) were not dependent upon the dose of F-ara-AMP. The area under the concentration X time curves for F-ara-A and F-ara-ATP, on the other hand, were increased in proportion to the prodrug dose. There was a high correlation between F-ara-ATP levels in circulating leukemic cells and those in bone marrow cells aspirated at the same time. DNA-synthetic capacity of leukemic cells was inversely related to the associated F-ara-ATP concentration. A linear trend was noted when F-ara-ATP levels in pretreatment peripheral blood leukemic cells incubated with F-ara-A in vitro were compared with the amount of F-ara-A that was incorporated into nucleic acids. Finally, F-ara-ATP concentrations were three times higher in bone marrow cells from patients with lymphomatous bone marrow involvement than from those without evidence of marrow disease.

Antimetabolites, Antineoplastic↗

PubMed1986

High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies.

We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m2-140 mg/m2) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.

Adult↗

PubMed1986

High dose therapy and autologous marrow transplantation as salvage treatment for patients with diffuse large cell lymphoma.

Twenty-nine patients with diffuse large cell lymphoma who failed traditional chemotherapy were treated with high dose chemotherapy with or without total body irradiation followed by infusion of cryopreserved autologous marrow. Complete response was achieved in 11/29 patients (38%), partial response in 13/29 patients (45%) and 5/29 patients (17%) had no response. Six complete responders remain well and free of disease for 5+, 6+, 9+, 10+, 18+ and 25+ months, 3 relapsed at 2, 3 and 8 months after marrow infusion, and 2 died from infectious complications. Complete response was seen more frequently with the absence of bulky tumor (70 vs 21%, P = 0.03), a total body irradiation containing regimen (52 vs 0%, P = 0.03), a history of complete remission with initial chemotherapy (55% vs. 9%, P = 0.03), and a performance status greater than or equal to 80 (56 vs 15%, P = 0.06). High dose therapy had a high response rate (83%) in resistant diffuse large cell lymphoma and yielded durable complete responses in a minority of these patients.

Adolescent↗

PubMed1986

A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma.

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.5 years. The minimum follow-up was 5.7 years. Seventy-five percent of the conventional-dose group achieved a complete remission (CR) with a 10-year actuarial survival of 53% and a corresponding relapse-free survival (RFS) of 69% for CRs. Eighty-one percent of the high-dose group achieved CR, and the 10-year actuarial survival for all patients and RFS for CRs were 48% and 63%, respectively. The combined actuarial survival and RFS for both groups were 51% and 66%, respectively, at 10 years. For 11 patients with stage III disease, 91% achieved CR, 52% survived at 10 years, and the RFS was 67% for CRs. Seventy-five percent of 44 patients with stage IV disease achieved CR, 50% survived at 10 years, and the RFS was 67% for CRs. Three of the 16 relapses occurred late, between 30 to 65 months after initiation of therapy. Neuropathy occurred in 14 patients (22%). Five patients (8%) died of complications related to treatment. Five (8%) had clinically apparent, but nonfatal cardiopulmonary complications. The CHOP-Bleo regimen is an effective treatment for diffuse large-cell lymphoma, and is moderately well tolerated. The use of high-dose CHOP-Bleo for induction therapy did not result in any advantage after long-term follow-up.

Adolescent↗