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F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 199 records · Page 11Linked to original sources

Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma.

After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases.

Antineoplastic Combined Chemotherapy Protocols↗

Accuracy of diagnosis of malignant lymphoma by combining fine-needle aspiration cytomorphology with immunocytochemistry and in selected cases, Southern blotting of aspirated cells: a tissue-controlled study of 86 patients.

Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is fraught with difficulty. In certain clinical situations, cytology has been documented to be useful in patients with malignant lymphoma. The intent of our investigation was to determine the accuracy of a multiparameter approach in diagnosing lymphoma. We reviewed the results of FNA cytology combined with the immunocytochemistry and, in some cases, the Southern blots of aspirated cell suspensions obtained from 86 suspected lymphoma patients who subsequently underwent surgical biopsy of the aspirated site. In four cases, in which FNA was unable to retrieve sufficient material for diagnosis, the histology showed extensive fibrosis. When the FNA diagnoses were compared with the histologic diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12 reactive, 1 atypical lymphoid proliferation). There was one false-positive, six false-negatives, and eight cases diagnosed as atypical lymphoid proliferation. Overall accuracy was 91%. There were two types of false-negative cases: those in which a diagnosis of another malignancy or unspecified malignant neoplasm was made and those that were diagnosed as reactive when the histology showed lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor genes were successfully performed on the aspirated cells and were useful in establishing lineage and clonality of both B and T lymphoid cells. Our study indicated that the use of a multiparameter approach in the diagnosis of malignant lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's lymphomas. In Hodgkin's disease, no benefit was derived from the approach.

Biopsy, Needle↗

Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease.

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.

Female↗

NOVP and radiotherapy for early-staged Hodgkin's disease: an interim analysis.

Modern treatment plans for early staged Hodgkin's disease must focus on optimal disease-free survival results without laparotomy, minimal acute toxicity, and reduced long-term complications. We have treated 69 adult patients with stage I-II Hodgkin's disease, 40 of whom had bulky disease, B symptoms, or hilar disease, and 22 with stage III disease with 3 cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) and radiotherapy. Only patients with stage III1 disease involving the celiac axis without para-aortic or pelvic involvement, had to undergo laparotomy prior to treatment. Three patients did not respond to NOVP: two of these did not respond to MOPP or ABDIC, and two are currently without relapse following bone marrow transplant. With a median follow-up of 18 months, 62 with stage I-II and 19 with stage III remain without relapse, and 91 patients are alive. Tolerance to therapy was excellent with minimal nausea, myalgias, and alopecia. We conclude that this regimen for Hodgkin's disease provides good results for clinically staged I-III disease, but longer follow-up may demonstrate prognostic factors which will influence our results.

Antineoplastic Combined Chemotherapy Protocols↗

Therapy of relapsed or refractory low-grade follicular lymphomas: factors associated with complete remission, survival and time to treatment failure.

Patients with relapsed low-grade follicular lymphomas (LGFL) frequently respond to subsequent therapy and can have long survival, but are rarely cured. Factors associated with complete remission (CR) rate, length of survival, and time to treatment failure (TTF) after relapse are not well known. We assessed such factors by multivariate analysis in a retrospective review of 95 patients with relapsed LGFL treated with investigational chemotherapy regimens at our institution. The CR rate after therapy was 22%; the likelihood of achieving CR was inversely associated with the number of previous treatment failures (P less than 0.001) and serum LDH level (P less than 0.05). Both the presence of constitutional symptoms and a history of more than two previous treatment failures were associated with shortened survival and TTF. Hemoglobin level was also significantly associated with survival. Prognostic models for survival and TTF were derived to define patient groups with different projected outcomes after therapy for relapsed disease. The results of this study can be used to select patients for new investigational treatments and to evaluate the outcome of such therapies.

Adult↗

A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the 'tumor score'.

A new staging system for intermediate grade lymphomas and immunoblastic lymphomas is described. This system is based on the tumor score which consists of assigning a point to each one of five variables that have been previously shown to have a high prognostic value. Ann Arbor stages III-IV, presence of bulky mass, elevation of B-2 microglobulin and LDH as well as presence of 'B' symptoms are the variables utilized in this system. When we applied this tumor score system to a population of 144 patients uniformly treated with CHOP/Bleo/CMED protocol, we observed that this system can accurately divide the population into two prognostic groups without an intermediate category. The first group is made up of those patients with a score of 0-2 points while the second group consists of patients with a score of > or = 3 points. The first group has a time-to-treatment failure (TTF) of 83% at three years in contrast to the second group whose TTF was 24%. If we compare this system with other commonly used systems in our institution, such as Ann Arbor, M.D. Anderson clinical staging system, and M.D. Anderson serological staging system, we observed that the tumor score system is not only more specific and sensitive than the others but also was capable of eliminating an intermediate risk group, thus facilitating therapeutic choices. This tumor score system is easy to apply and potentially reproducible in any institution.

Adolescent↗

Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma.

PURPOSE: In a phase II trial we investigated fludarabine phosphate (FAMP) as therapy for patients with relapsed lymphoma to determine its effectiveness and toxicity in this disease. PATIENTS AND METHODS: The 67 assessable patients had a median age of 56 years and had received a median of three chemotherapy regimens before treatment with FAMP. The starting dose was 25 mg/m2 administered intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS: High response rates were observed for follicular small cleaved-cell lymphoma (FSCCL) (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and Hodgkin's disease (25%). No responses were observed in other intermediate- or high-grade lymphomas (N = 20). Overall, there were five patients with a complete response, 23 patients with a partial response, and an overall response rate of 37%. Toxicity was primarily hematologic and infectious. No significant gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS: We conclude that FAMP has major activity in follicular lymphoma. Fundamental research is needed to understand this differential efficacy in low-grade lymphoma yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical investigations should be done using FAMP in varying dose schedules and in combination regimens.

Adult↗

Non-Hodgkin's lymphomas: a review of the M.D. Anderson experience.

The approach we have followed in developing treatment strategies for lymphoma consists of testing new combinations in patients with recurrent disease and, if these are found to be effective, advancing them to front-line therapy. Three series of salvage regimens tested at the M. D. Anderson Cancer Center (MDACC) will be described. These were initially based on ifosfamide/etoposide, later on high-dose cytarabine/cisplatin, and more recently on a novel strategy that first uses MINE (mesna/ifosfamide/Novantrone [mitoxantrone; Lederle International, Wayne, NJ]/etoposide) for induction of remission and, following the attainment of the maximum response to MINE, changes treatment to a non--cross-resistant combination known as ESHAP (etoposide/Solu-medrol ([methylprednisolone]/high-dose cytarabine/cisplatin). The front-line management of intermediate-grade lymphoma at MDACC currently is based on prognostic factors. The criteria for selecting categories of less favorable patients will be discussed. A new regimen, alternating triple therapy based on three non--cross-resistant drug regimens, currently is being explored for these patients. Already this regimen has shown an early advantage in the worst category of cases, those with M.D. Anderson stage D (high tumor burden, high levels of lactate dehydrogenase). The data, however, remain preliminary.

Adult↗

Prognostic value of serum beta-2 microglobulin in low-grade lymphoma.

OBJECTIVE: To evaluate serum beta-2 microglobulin (beta-2M) and other prognostic indicators in previously untreated low-grade lymphoma. DESIGN: Cohort study of 80 patients with uniformly treated low-grade lymphoma, followed for a median of 21 months. These 80 patients, all of whom had serum beta-2M drawn within 2 weeks before starting therapy, were derived from a cohort of 119 previously untreated patients entered into one of three clinical trials. SETTING: Tertiary referral cancer center. PATIENTS: Eighty previously untreated stage I to IV patients (mean age, 55 years). INTERVENTION: Treatment was given according to Ann Arbor stage: Patients in stage IV were treated with CHOP-bleomycin and maintained on interferon therapy; those in stage III received CHOP-bleomycin and radiotherapy; and those in stages I and II received COP-bleomycin and radiotherapy. MEASUREMENTS: Outcome was determined by assessing complete remission rate and time to treatment failure. Univariate and multivariate analyses were used. RESULTS: The complete remission rate for patients with a beta-2M level of 3.0 mg/L or greater was 36% compared with 71% for those with a level of less than 3.0 mg/L. Using multivariate analysis that tested beta-2M as a continuous variable, it was selected as the most significant factor for complete response. The adjusted odds ratio was 0.285 (95% CI, 0.101 to 0.809). The Ann Arbor stage had marginal significance (adjusted odds ratio, 0.435; CI, 0.150 to 1.263). For time to treatment failure, beta-2M was the only variable retained in the multivariate model. At 42 months, no patient with a beta-2M level of 3.0 mg/L or greater was projected to be in remission as compared with 85% of patients with a beta-2M level of less than 3.0 mg/L. CONCLUSIONS: The serum beta-2M level is a good predictor of complete response and time to treatment failure. A larger number of patients should be studied to clarify the role of other potentially independent variables such as stage and age.

Adult↗

Stage I-II low-grade lymphomas: a prospective trial of combination chemotherapy and radiotherapy.

Between 1984-1989, 44 patients with stage I-II low grade lymphoma were treated prospectively with sequential chemotherapy and involved-field radiotherapy. The chemotherapy was cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo); doxorubicin was included (CHOP-Bleo) for patients with adverse prognostic features (high LDH; extranodal sites; bulky nodes). Of the 44 patients, 37 had measurable disease and all have responded. With a median follow-up of 32 months, the 5-year survival and failure-free survival were 89% and 74%, respectively. Compared to past experience with involved-field radiotherapy alone, the failure-free survival is significantly better with COP-Bleo plus radiotherapy. The potentially cured fraction has risen from 40% to 74%.

Adult↗

Experience with salvage regimens at M.D. Anderson Hospital.

With the intent of using active regimens in the front-line setting, new combinations of chemotherapy have been tested as salvage treatment in lymphoma patients at M.D. Anderson Hospital. Combinations based on ifosfamide plus etoposide, including IMVP-16 (ifosfamide/methotrexate/etoposide) and MIME (methyl-GAG/ifosfamide/methotrexate/etoposide) resulted in overall and complete responses (CRs) of 60 and 25%, respectively. Long-term follow-up of MIME indicates a 25% cure rate in intermediate-grade lymphoma patients who achieve CR. The in vitro synergism of platinum and high-dose cytarabine recently has been confirmed clinically. A study is currently under way to evaluate the effect of integrating MINE (mesna/ifosfamide/mitoxantrone/etoposide) and ESHAP (etoposide/methyl prednisolone/cytarabine/platinum) into one protocol.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of non-Hodgkin's lymphoma.

Many of the advances in the management of non-Hodgkin's lymphomas have been based on more precise understanding of the various cell types that constitute these disorders. During the past year, we have seen some dramatic changes in the therapeutic approach to low-grade lymphomas. Until recently, the usual approach to these disorders was a purely palliative one, but a number of publications from the past year describe a more intensive approach with the goal of developing a curative modality. The use of combination chemotherapy in addition to radiation therapy for the early Ann Arbor stages as well as the use of high-dose chemotherapy with bone marrow transplantation in patients with high-risk factors has been reported recently. In the area of intermediate-grade lymphomas, most of the recent publications have described prognostic factors associated with various chemotherapy protocols. One of the most interesting recent developments is related to the dose-intensity issue. A consensus appears to be developing in regard to the correlation of dose intensity with clinical outcome. Despite the fact that new third-generation regimens have been associated with cures in 50% to 66% of the patients, a significant fraction of patients require salvage chemotherapy. Some of the new salvage regimens are discussed, as is the use of calcium channel blockers to reverse multiple-drug resistance. Finally, management of the high-grade lymphomas, specifically the small noncleaved cell type, has been associated with a cure rate in the range of 50% in two recently published studies. Patients who are human immunodeficiency virus-positive with small noncleaved cell lymphoma can be cured of their underlying malignancy, but many of them later develop complications of acquired immunodeficiency syndrome, to which they usually succumb.

Acquired Immunodeficiency Syndrome↗

Chromosome 17- and p53 changes in lymphoma.

The clinical course of lymphoma patients in whom rearrangements or deletions of the short arm of chromosome 17 (17p) were evident by cytogenetics was rapidly progressive with a short survival. The gene for the protein designated p53 resides in 17p. We studied four lymphoma cell lines derived from human tumours, and 25 tumour samples of patients with lymphomas, for any evidence of p53 genomic changes by Southern blot technique. The four cell lines and four of the 25 tumour samples showed numerical changes of chromosome 17 or structural abnormalities of 17p (translocations or deletions). Allelic loss of the p53 gene was found in two of the four cell lines, and one of these in addition showed a rearrangement of the 3' end of the gene. Of the four tumours known to have chromosome 17 abnormality, one specimen showed allelic loss of the p53 gene. None of the remaining tumour samples showed any significant change. These studies suggest that acquisition of changes in the short arm of chromosome 17, which may be interrelated with the p53 gene, may carry a poor prognosis in patients with non-Hodgkin's lymphoma.

Adult↗

Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.

We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials.

Antineoplastic Combined Chemotherapy Protocols↗

Surgical debulking is associated with improved survival in stage I-II diffuse large cell lymphoma.

Tumor burden is an important predictor of survival in patients with diffuse large cell lymphoma (DLCL). The authors reviewed the charts of 147 patients with early stage presentation (Stage I-IE and II-IIE) seen from 1974 through 1984. The 10-year survival for the 85 patients with bulky disease was 54% compared with 76% for those who did not have bulky disease. Of the 62 with nonbulky disease, 14 had been rendered so by removal of greater than 80% of the initial tumor mass (surgical debulking). The authors compared these 14 patients with a matched control group of 14 patients selected from the 85 with bulky disease who had equivalent stage, therapy, site, size of initial mass, performance status, and sex and age. All had received similar therapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, prednisone, bleomycin, and radiotherapy to the involved field. At a 7-year follow-up, the 14 debulked patients had a better survival when compared with the matched controls (93% versus 35%, P = 0.003). The authors also analyzed the initial serum lactate dehydrogenase (LDH) levels. Preoperative LDH values were available in six of 14 debulked patients. In the three with elevated LDH levels at presentation, surgical debulking was associated with subsequent decreased LDH levels, which is known to be associated with better prognosis. The other three presented with normal values that remained normal after surgery. These data suggest a potentially important role for surgery as front-line therapy in patients with Stage I-IE and II-IIE bulky DLCL whose disease is deemed resectable. More studies are needed in order to better define this role as well as to determine how frequently and safely surgical debulking can be performed.

Adult↗