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Fernando Cabanillas

Publications and source records attributed to Fernando Cabanillas.

At least 37 records · Page 2Linked to original sources
PubMed2003

Central lymphatic irradiation for stage I-III follicular lymphoma: report from a single-institutional prospective study.

PURPOSE: This study was undertaken to update our experience with follicular lymphoma treated with central lymphatic irradiation (CLI). METHODS AND MATERIALS: A total of 47 patients were treated with CLI between January 1993 and March 2000 in a prospective manner. CLI consisted of mantle, whole abdomen, and pelvic radiation fields with a 1-month break after each field. Each field was treated to 3000-3060 cGy at 150-180 cGy per fraction followed by a boost dose of 900 cGy to the areas with gross disease. The median age was 52 years (range: 29-73 years). There were 29 males. The diagnoses were as follows: follicular small cleaved-cell lymphoma, 23 patients; follicular mixed-cell lymphoma, 19 patients; follicular large-cell lymphoma, 5 patients. Ann Arbor stages were as follows: I, 5 patients; II, 14 patients; and III, 28 patients. The International Prognostic Index (IPI) categories were as follows: 0, 14 patients; 1, 24 patients; and 2, 9 patients. M. D. Anderson Tumor Score was as follows: 0, 14 patients; 1, 18 patients; 2, 9 patients; 3, 4 patients; 4, 1 patient; and unknown, 1 patient. Two patients had abnormal LDH levels, and 11 patients had beta2M levels >2 mg/dL. Gender, pathology, stage, IPI, Anderson Tumor Score, beta2M, and number of disease sites were examined for significance in freedom from progression (FFP) by univariate analyses. RESULTS: The median follow-up was 54 months (range: 8-93 months) for the 45 surviving patients. Every patient achieved a complete response, except for 1 patient whose lymphoma progressed to diffuse large-cell lymphoma during treatment. The 5-year overall survival and FFP were 94% and 53%, respectively. No failure has yet been observed beyond 55 months of follow-up with 13 patients at risk. Patterns of failure were as follows: within the radiation field, 10; outside the fields, 4; and both, 2. Of the seven variables investigated, beta2M >2 mg/dL and IPI >1 were the only significant adverse prognostic factors for FFP (p = 0.023 and 0.046, respectively). CONCLUSIONS: CLI is well tolerated and seems to achieve durable FFP in about half of the patients with Stage I-III follicular lymphoma. Most of the experiences with CLI come from the treatment of Stage III disease and are very similar to our previous experience with combined modality treatment. Whether a plateau in FFP can be maintained beyond 5 years remains to be seen.

Adult↗
PubMed2003

Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy.

BACKGROUND: The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS: Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS: Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.

Adult↗
PubMed2003

Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE: Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS: A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS: The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.

Adult↗
PubMed2003

Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma.

BACKGROUND: The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15-30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown. METHODS: From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations. RESULTS: Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients. CONCLUSIONS: Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study.

Adult↗
PubMed2003

Analysis of in-field control and late toxicity for adults with early-stage Hodgkin's disease treated with chemotherapy followed by radiotherapy.

PURPOSE: We analyzed in-field (IF) control in adults with early-stage Hodgkin's disease who received chemotherapy followed by radiotherapy (RT) in terms of the (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to chemotherapy, and (3) initial tumor size. Cardiac toxicity and second malignancies, particularly the incidence of solid tumors in terms of the RT field size treated, were also examined. METHODS AND MATERIALS: From 1980 to 1995, 286 patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4 weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP, MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161, 67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3) cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of disease were included in the RT fields. The median prescribed RT dose for gross disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little variation in the RT dose. Eighty-five patients were treated with involved-field or regional RT (to one side of the diaphragm), and 201 patients were treated with extended-field RT (to both sides of the diaphragm), based on the protocol on which they were enrolled. RESULTS: Follow-up of surviving patients ranged from 1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films, there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The chemotherapeutic regimen used and the number of cycles of chemotherapy delivered did not significantly affect IF control. IF control also did not significantly depend on the response to induction chemotherapy. In cases where there was a confirmed or unconfirmed complete response as opposed to a partial response or stable disease in response to induction chemotherapy for bulky nodal disease, the 5-year IF control rates were 99% and 92%, respectively (p = 0.0006). The 15-year actuarial risks of coronary artery disease requiring surgical intervention and of solid tumors were 4.1% and 16.8%, respectively. There was a trend toward a greater risk of solid tumors in patients who received extended-field RT rather than involved-field or regional RT (p = 0.08). CONCLUSIONS: In patients with nonbulky disease, induction chemotherapy followed by RT to a median dose of 40.0 Gy resulted in excellent IF control, regardless of the chemotherapeutic regimen used, the fact that only 1-2 cycles of chemotherapy were delivered, and the response to chemotherapy. There was a trend toward a higher incidence of solid tumors in patients who received consolidation RT to both sides rather than only one side of the diaphragm. Ongoing Phase III trials will help clarify whether lower RT doses and smaller RT fields after chemotherapy can maintain the IF control seen in our study, but with a lower incidence of late complications in patients with Stage I or II Hodgkin's disease.

Adolescent↗
PubMed2003

Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.

PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.

Adult↗
PubMed2003

Prognostic significance of MUC-1 expression in systemic anaplastic large cell lymphoma.

Systemic anaplastic large cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) and overexpresses anaplastic lymphoma kinase (ALK). MUC-1, a highly glycosylated transmembrane protein, is detected in normal and malignant epithelial cells and has been associated with a poorer patient survival in various human malignancies. We have shown previously that MUC-1 is expressed as a consequence of t(1;14)(q21;32) in a subset of diffuse large B-cell lymphomas. ALCLs are known to express MUC-1, but its clinical significance is undefined. For this study, eligible patients with ALCL were HIV negative, received anthracycline-containing regimens, and had pretreatment archival tissue. Expression of MUC-1 and ALK was determined immunohistochemically after heat-induced antigen retrieval. A 10% cutoff for MUC-1 positivity was used. We identified 63 patients with systemic ALCL (22 ALK+, 41 ALK-) with a median age of 47 years, and 41 were male. MUC-1 was detected in 16 of 22 (73%) ALK-positive and 20 of 41 (49%) ALK-negative ALCL (P = 0.06, chi(2) test). MUC-1 expression was not associated with apoptotic rate as detected by terminal deoxynucleotidyl transferase-mediated nick end labeling assay or proliferation index as evaluated by MIB-1 antibody. For 48 patients with ALCL (16 ALK+, 32 ALK-) and complete clinical follow-up, 5-year progression-free survival (PFS) was 39.7% for patients with MUC-1-positive tumors versus 75.2% (P = 0.027 by Log-rank) for patients with MUC-1-negative tumors. For the ALK-negative ALCL group of 32 patients, the 5-year PFS was 26 versus 70.8% for patients with MUC-1-positive versus MUC-1-negative tumors (P = 0.0096 by Log-rank). For the ALK-positive ALCL group of 16 patients, the 5-year PFS was 52 versus 100% for patients with MUC-1-positive versus MUC-1-negative tumors (P, not significant). In summary, MUC-1 is frequently expressed in systemic ALCL, and its expression is associated with significantly inferior outcome in patients untreated previously with ALK-negative tumors. Future studies should explore the underlying molecular mechanisms of MUC-1 expression in these tumors and its role as a target for novel therapeutic strategies.

Adolescent↗
PubMed2002

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

BACKGROUND: The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. METHODS: From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). RESULTS: Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). CONCLUSIONS: The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials.

Adolescent↗
PubMed2002

BCL-2 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease predicts a poorer prognosis in patients treated with ABVD or equivalent regimens.

To determine the clinical significance of BCL-2 expression in Hodgkin-Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD), we correlated its expression with presenting clinical and laboratory features and failure-free survival (FFS). Eligible patients were untreated and negative for HIV-1; they had biopsy-proven cHD. BCL-2 expression was determined immunohistochemically in available pretreatment tissue biopsy specimens without knowledge of clinical outcome. Tumors were considered positive if any HRS cells expressed BCL-2. We identified 707 patients with cHD, whose median age was 30 years; 54% were men. HRS cells expressed BCL-2 in 359 (65%) of 551 nodular sclerosis, 67 (47%) of 143 mixed cellularity, and all 5 lymphocyte depletion. For all patients, the 5-year FFS was 74% versus 84% for tumors with versus without BCL-2 expression (P =.0016, by log-rank test). For the 412 patients treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens, the 5-year FFS for tumors with versus without BCL-2 expression was 74% versus 88% (P =.001, by log-rank test); for the 233 patients with Ann Arbor stage I or II, FFS was 84% versus 92% (P =.04, by log-rank test); and for the 179 patients with Ann Arbor stage III or IV, FFS was 62% versus 81% (P =.006, by log-rank test). Multivariate analysis confirmed that BCL-2 expression is independently associated with inferior FFS along with age 45 or older, Ann Arbor stage IV, low serum albumin and high serum lactate dehydrogenase levels. We conclude that BCL-2 is frequently expressed by HRS cells in cHD and is associated with inferior FFS in patients treated with ABVD or equivalent regimens.

Adolescent↗
PubMed2002

Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma.

Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P =.9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P =.9); the 5-year FFS rates were 41% with FND and 50% with ATT (P =.02). In a multivariate analysis, factors predicting for longer FFS were beta(2)-microglobulin less than 3 mg/L (P =.01) and ATT treatment (P =.03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND.

Adult↗
PubMed2002

International prognostic index-based outcomes for diffuse large B-cell lymphomas.

BACKGROUND: We present the results of doxorubicin-based chemotherapy with or without involved-field radiotherapy for patients with diffuse large B-cell lymphoma (DLBCL) according to the international prognostic index (IPI). METHODS: From September 1988 through December 1996, 294 patients with Stage I-IV Working Formulation large B-cell or T-cell lymphomas were treated prospectively on two protocols at our center. Diagnoses were reclassified subsequently according to the new World Health Organization classification. Two-hundred and twenty-four patients had DLBCL, including 24 patients with primary mediastinal large B-cell lymphoma. Treatment consisted of a median of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy with or without involved-field radiotherapy (median dose, 39.6 Gy). RESULTS/CONCLUSIONS: The median length of follow-up among surviving patients was 5.0 years. Patient subgroups differed from each other in terms of progression-free (P = 0.003), cause-specific (P = 0.003), and overall (P = 0.001) survival rates when analyzed by IPI. Five-year progression-free, cause-specific, and overall survival rates for 212 patients with an IPI of 0-2 were 73%, 84%, and 82%, respectively, versus only 37%, 33%, and 32% for 12 patients with an IPI of 3-4. To improve our results, we are conducting clinical trials with young DLBCL patients and with patients who are older than 60 years. The young DLBCL patients, who have more than two adverse prognostic features, are receiving high-dose chemotherapy and autologous stem cell rescue. The patients who are older than 60 years, regardless of IPI, are receiving rituximab immunotherapy and liposomal CHOP chemotherapy with or without involved-field radiotherapy.

Adolescent↗
PubMed2002

Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL. PATIENTS AND METHODS: Patients received either a single intravenous (IV) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel. RESULTS: ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56% for the rituximab group (P =.002). Complete response (CR) rates were 30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group (P =.6), and time to progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable responses of > or = 6 months were 64% versus 47% (P =.030). Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan. CONCLUSION: Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.

Adult↗
PubMed2002

European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS: The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients.

Adolescent↗
PubMed2002

CD20 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin's disease: associations with presenting features and clinical outcome.

PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD), but its clinical significance remains controversial. Therefore, we correlated CD20 expression with presenting features and clinical outcome of untreated patients with classical HD. PATIENTS AND METHODS: Patients were eligible if they were previously untreated and human immunodeficiency virus-1 negative, had biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor tissue was available. CD20 expression was determined by immunohistochemistry without knowledge of clinical outcome. A tumor was considered positive if any HRS cells expressed CD20, but other cutoffs for number of CD20-positive HRS were also investigated. RESULTS: We identified 598 patients whose median age was 30 years and of whom 55% were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with classical HD. When any percentage of CD20 expression in HRS cells was used as a cutoff, the 5-year failure-free survival (FFS) for positive versus negative tumors was 86% versus 84%, respectively, for 302 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens (P =.7 by log-rank test), 74% versus 77%, respectively, for 181 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P =.7 by log-rank test), 74% versus 84%, respectively, for 54 patients treated with MOPP (P =.4 by log-rank test), and 77% versus 88% for 53 patients treated only with radiotherapy (P =.5 by log-rank test). The 5-year FFS was not statistically different when cutoffs of 5% up to 50% for CD20-positive HRS cells were used. CONCLUSION: CD20 is expressed by HRS cells in 22% of patients with classical HD but is not associated with different FFS after treatment with equivalent regimens.

Adolescent↗
PubMed2002

Results with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy with or without prechemotherapy surgical debulking for patients with bulky, aggressive lymphoma.

BACKGROUND: The authors performed a case-control analysis of local control, progression free survival, and overall survival in patients with Stage I-II aggressive lymphomas measuring > or = 7 cm in greatest dimension who were treated initially with or without surgical debulking: All patients then received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) based chemotherapy followed by involved field radiotherapy. METHODS: From May 1975 through May 1996, 50 patients were treated with (n = 25 patients) or without (n = 25 patients) resection of > 80% of their bulky lymphomas. Chemotherapy consisted of 3-12 cycles of CHOP. In general, patients who underwent debulking received three cycles of chemotherapy, whereas patients who did not undergo debulking received at least six cycles of chemotherapy. The total radiotherapy dose was 40.8 grays (Gy) +/- 4.2 Gy (mean +/- standard deviation). RESULTS: The median follow-up was 62 months. Patients who underwent debulking were similar prognostically to patients who did not. There was a trend toward improved local control (5 year rates: 96% vs. 80%; P = 0.10) and overall survival (5 year rates: 83% vs. 71%; P = 0.18) in patients who underwent debulking compared with patients who did not, respectively. Progression free survival was significantly better for patients who underwent debulking compared with patients who did not (5 year rates: 88% vs. 62%, respectively; P = 0.04). CONCLUSIONS: Because this study was retrospective, selection bias may account for the observed difference in progression free survival. Because it is unlikely that a trial randomizing patients with bulky, aggressive lymphoma to surgery will be conducted, the authors' current efforts are focused on escalation of the total radiotherapy dose as a possibly less costly and less morbid approach toward improving progression free survival for these patients.

Aged↗
PubMed2002

Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodgkin disease: potential therapeutic significance.

BACKGROUND: The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express CD30 and CD40 receptors that can activate nuclear factor kappa B and transduce survival signals. The authors have reported previously that the B lymphocytes of HD express CD30 ligand (CD30L, CD153). Furthermore, they and others have reported previously that the CD40L survival pathway is augmented in patients with B-cell malignancies, as CD40L was constitutively expressed by the malignant B cells and infiltrating T cells, and sera from those patients contained elevated levels of soluble CD40L. In this study, the authors investigated the hypothesis that the survival of H/RS cells was similarly promoted by an augmented CD40L signals in HD patients. METHODS: The expression of CD40L on lymphocyte subsets of patients with classic HD was determined by two-color fluorescent-activated cell sorter analysis. Serum soluble CD40L levels were determined by enzyme linked immunosorbent assay. RESULTS: CD40L was constitutively expressed on both the T and B cells of HD patients but was more prominently expressed on the B lymphocytes. Soluble CD40L was detected in the serum of 17 of 37 patients (45%) and was higher than 1 ng/mL in 4 patients (10%). Both interleukin (IL)-4 and IL-10, which are known to be secreted by H/RS cells and surrounding T cells, up-regulated CD40L expression on normal B cells. CONCLUSIONS: Thus, the expression of CD40L and CD30L on the B cells of HD patients suggests that B lymphocytes may play a role in the regulation of H/RS cell growth in vivo. Depriving H/RS cells from CD30L and CD40L survival signals by eliminating B cells from HD lesions may be of therapeutic value.

B-Lymphocytes↗