Seroprevalence of HPV 6, 11, 16 and 18 and correlates of exposure in unvaccinated women aged 16-64 years in Puerto Rico.

BACKGROUND: To understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area. METHODS: As part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16-64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR. RESULTS: 32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 - 29%, HPV11 - 18%, HPV16 - 23%, and HPV18 - 17%; seroprevalence was high in the youngest age-group (16-19: 26-37%). HPV seropositivity was associated with having ≥ 3 lifetime sexual partners (OR=2.5, 95% CI=1.7-3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2-2.6). CONCLUSIONS: The high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16.

Factors Associated with HPV Vaccine Awareness in a Population-Based Sample of Hispanic Women in Puerto Rico.

OBJECTIVES: The objective of this study was to investigate the factors associated with HPV awareness among women aged 16 to 64 years, among underserved minority Hispanic women living in Puerto Rico. METHODS: A population-based, cross-sectional sample of 566 women, ages 16 to 64 years, living in the San Juan metropolitan area were surveyed regarding sexual behavior, HPV knowledge, and HPV vaccine uptake. Data was analyzed using descriptive statistics and multivariate logistic regression. RESULTS: Overall, 64.8 % of the women in the sample had heard about the HPV vaccine. Among those in the recommended catch-up vaccination age range (16-26 years, n = 86), 4.7 % had received at least one dose of the HPV vaccine. Of those aware of the availability of the HPV vaccine, most had learned about it through the media, whereas, only 39.6 % had learned about it from a physician. Multivariate logistic regression analysis showed that HPV awareness (OR 8.6; 95 % CI 5.0-14.8) and having had an abnormal Pap smear (OR 2.0; 95 % CI 1.2-3.4) were associated with HPV vaccine awareness (p < 0.05). CONCLUSION: HPV vaccine awareness among Hispanic women in the San Juan metropolitan area of Puerto Rico continues to be low. Strong recommendations from physicians and participation in HPV vaccine educational efforts are essential if the rate of HPV vaccination is to increase in the targeted population. Compared to the USA, and to their US Hispanic counterparts, a health disparity with regard to HPV vaccine awareness and coverage is evident in Puerto Rico; targeted action to deal with this disparity is urgently needed.

Patients with classical Hodgkin lymphoma experiencing disease progression after treatment with brentuximab vedotin have poor outcomes.

BACKGROUND: Brentuximab vedotin (BV) is a key therapeutic agent for patients with relapsed/refractory classical Hodgkin lymphoma (cHL). The outcomes of patients experiencing disease progression after BV are poorly described. PATIENTS AND METHODS: We reviewed our institutional database to identify patients with cHL treated with BV who were either refractory to treatment or experienced disease relapse. We collected clinicopathologic features, treatment details at progression and outcome. RESULTS: One hundred patients met inclusion criteria, with a median age of 32 years (range 18-84) at progression after BV. The median number of treatments before BV was 3 (range 0-9); 71 had prior autologous stem cell transplant. The overall response rate (ORR) to BV was 57%, and the median duration of BV therapy was 3 months (range 1-25). After disease progression post-BV, the most common treatment strategies were investigational agents (n = 30), gemcitabine (n = 15) and bendamustine (n = 12). The cumulative ORR to therapy was 33% (complete response 15%). After a median follow-up of 25 months (range 1-74), the median progression-free (PFS) and overall survival (OS) were 3.5 and 25.2 months, respectively. In multivariate analysis, no factors analyzed were predictive of PFS; age at progression >45 years and serum albumin <40 g/l at disease progression were associated with increased risk of death. Among patients who achieved response to therapy, allogeneic stem cell transplantation was associated with a non-significant trend toward superior OS (P = 0.11). CONCLUSIONS: Patients with BV-resistant cHL have poor outcomes. These data serve as a reference for newer agents active in BV-resistant disease.

Factors influencing outcome in advanced stage, low-grade follicular lymphoma treated at MD Anderson Cancer Center in the rituximab era.

BACKGROUND: The optimal initial therapy of follicular lymphoma (FL) remains unclear. The aims of this study were to compare primary treatment strategies and assess the impact of maintenance rituximab and patterns of treatment failure. PATIENTS AND METHODS: We retrospectively analyzed patients with treatment-naive advanced stage, grade 1-2 FL treated at our center from 2004 to 2014. We included 356 patients treated on clinical trials or standard of care with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP, n = 119); R-CHOP with maintenance (R-CHOP + M, n = 65); bendamustine/rituximab (BR, n = 45); BR with maintenance (BR + M, n = 35); R(2) (n = 94). We compared baseline characteristics, progression-free survival (PFS), overall survival (OS) and analyzed prognostic factors using univariate and multivariate analysis adjusted for treatment. RESULTS: After a median follow-up of 4 years (range 0.2-15.0), the 3-year PFS was 60% [95% confidence interval (CI) 51% to 69%] for R-CHOP, 72% (59% to 82%) for R-CHOP + M, 63% (42% to 78%) for BR, 97% (80% to 100%) for BR + M and 87% (78% to 93%) for R(2). Patients treated with R-chemotherapy had more high-risk features than patients treated with R(2) but, by adjusted multivariate analysis, treatment with R(2) [hazard ratio (HR) 0.39 (0.17-0.89), P = 0.02] was associated with a superior PFS. Eastern Cooperative Oncology Group Performance status of one or more predicted inferior OS. Among patients treated with R-chemotherapy, maintenance was associated with the superior PFS [HR 0.38 (95% CI 0.21-0.68)]. By adjusted multivariate analysis, disease progression within 2 years [HR 5.1 (95% CI 1.57-16.83)] and histologic transformation (HT) [HR 11.05 (95% CI 2.84-42.93)] increased risk of death. CONCLUSION: Induction therapy with R(2) may result in disease control which is comparable with R-chemotherapy. Early disease progression and HT are predictive of inferior survival.

Prevalence, genotyping, and correlates of anogenital HPV infection in a population-based sample of women in Puerto Rico.

BACKGROUND: Oncogenic HPV infection is associated to anogenital cancer. We estimate the prevalence and correlates of anogenital HPV infection among a population-based sample of women aged 16-64 years living in the metropolitan area of Puerto Rico. METHODS: 564 women completed face-to-face and computer assisted interviews and self-collected anal and cervical specimens. HPV DNA testing used MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for sample amplification. Positive specimens were typed by dot-blot hybridization. RESULTS: Weighted prevalence of cervical, anal, and cervical/anal co-infection was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%), correspondingly. Having ≥3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5-3.5) and last year anal intercourse (OR: 1.6; 95% CI: 1.1-2.5) increased the odds of anogenital HPV infection. Cervical infection was independently associated to anal infection (OR: 3.0; 95% CI: 2.0-4.6). CONCLUSIONS: Similar to others, our results confirm the burden of anogenital HPV infection in women and its relationship with sexual behavior. As vaccination increases, future studies should monitor changing trends in HPV infection in this population, and the relationship between anal and cervical HPV-related disease.

Use of Screening Tests for Colorectal Cancer Among Gynecologists in Puerto Rico.

OBJECTIVE: To determine the use of screening tests for colorectal cancer (CRC) among Gynecologists in Puerto Rico. This study evaluates the screening practices used by Gynecologists in PR to diagnose CRC and adherence to screening guidelines. METHODS: A self-administered anonymous questionnaire was mailed to 440 practicing gynecologists through the College of Physicians and Surgeons of PR. The questionnaire included general and specific questions. RESULTS: Response rate was 23.2% (102/440). Of this group of gynecologists, 77.5% referred screening patients, while 22.5% did not. The majority (28.4%) use Fecal Occult Blood Test (FOBT) as a first screening test, while 27.5% use Colonoscopy. Screening is started by 49% at age 50. Only 7% stop screening at 75 years and 31% never stop screening. CRC Screening performed by participants were: 35% screen annually, 6% screen 2-3 years, 10% screen every 5 years, 6% screen every 10 years and 6% screen 5-10 years. Data for CRC Screening reveals 7% gynecologists comply with all the guidelines; 49% comply with the recommendations regarding the start screening age and 7% stop screening as per guidelines. CONCLUSION: The recommendations are not followed by most of the gynecologists in PR that participated in the study, Further research should be directed towards the reasons for not complying and how to educatethemedical population to achieve adequate screening in the PR female population.

Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes.

BACKGROUND: Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown. PATIENTS AND METHODS: We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study. RESULTS: We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS. CONCLUSION: The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed.

Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial.

Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7-52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide-rituximab is associated with prolonged response duration.

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma.

BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had (111)In ibritumomab tixuetan imaging to confirm expected biodistribution before (90)Y-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. RESULTS: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was <3 Gy, 10 times lower than that with EBRT. CONCLUSIONS: Rituximab followed by (90)Y ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.

Relationship between loss of libido and signs and symptoms of depression in a sample of Puerto Rican middle-aged women

Female sexual dysfunction is a multi-causal and multidimensional problem combining sexual, physiological, physical, psychological, and interpersonal determinants. Loss of libido or loss of sexual desire, as a symptom of one of the primary sexual dysfunctions described in females, is highly prevalent in the general female population. Research on the psychological aspect associated with loss of libido among Hispanic female populations is limited. The objective of this study was to determine how the loss of libido is affected by signs and symptoms of depression, once potential confounders are controlled. Nine-hundred and nineteen Puerto Rican women ages 40 to 59 years living in Puerto Rico participated in health-fairs conducted in twenty-two municipalities between May 2000 and November 2001. Contingency tables and chi-square statistics were used to evaluate the bivariate associations of loss of libido with demographic and lifestyle characteristics, symptom experience and obstetric and gynecologic histories. A logistic regression model was used to estimate the magnitude of the association between loss of libido and signs and symptoms of depression, after controlling for confounders. The overall prevalence of loss of libido in this population was 40.8%. Loss of libido was significantly associated with depressive symptoms (p < 0.05) after adjusting for age, educational attainment, employment status, physical activity, menopausal status/ hormone therapy use and genitourinary symptoms. Women reporting 1-2 depressive symptoms were 67% (95% CI = 1.08-2.60) more likely than women reporting no symptomatology to report loss of libido. The odds of loss of libido increased as the number of depressive symptoms increased [(3-4 symptoms: POR = 3.67, 95% CI = 2.16-5.56); (5-6 symptoms: POR = 5.52, 95% CI = 3.16-9.66)]. Consistent with previous studies, signs and symptoms of depression were significantly associated with loss of libido. Future longitudinal studies should...

The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma.

BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. RESULTS: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although front therapy induces a high rate of complete remission (CR), relapse is inevitable and new regimens are much needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but CR rates are low, with a short duration of response and severe toxicity. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX). Increasing doses of BTZ with a fixed dose of RTX and CTX (BRC regimen) resulted in markedly synergistic growth inhibition of MCL cells. BRC significantly enhanced apoptosis in MCL cell lines and primary tumor cells compared with single-agent treatment. Furthermore, western blotting analysis indicated that BRC induces apoptosis earlier via activation and cleavage of caspases-8, -9 and -3, and poly (ADP-ribose) polymerase, than single-agent treatment. The pan-caspase inhibitor completely blocked apoptosis induced by BRC. In vivo studies showed that BRC eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the long-term event-free survival in 70% of the mice. Hence, our study demonstrates that cytoreductive chemotherapy with both BTZ and anti-CD20 antibody may offer a better therapeutic modality for relapsed MCL.

Depressive symptoms and risk factors among perimenopausal women

BACKGROUND: Several studies indicate that approximately 4.6of the Puerto Rican Population has been affected by depression at some time in their life. Perimenopausal women have been one of the most frequently mentioned population in scientific literature prone to develop depression. Sociodemographic factors along with medical history have been hypothesized to be associated with the development of depression. This study has the purpose to know the prevalence of depressive symptoms in a sample of women age 40 to 55 years attending a gynecological outpatient clinic in the Medical Sciences Campus of the University of Puerto Rico. We also want to identify sociodemographic risk factors that can predispose these women to develop depressive symptoms. METHOD: A cross sectional study was done during the months of June 2000 thru December 2000. Female subjects age 40 to 55 selected by availability. The Zung Self-Rating Depression Scale (1995 Spanish Version) and a questionnaire were administered to each subject. Results. The overall prevalence of depressive symptoms in this sample of 64 women was 39.1. Among the variables considered as possible associated risk factors for the development of depressive symptoms, educational level, prior visit to a mental health professional or a spiritual guide, and prior diagnosis of depression and antidepressant use were of statistical significance. DISCUSSION: A high prevalence of depressive symptoms was found in this sample. As reported in other studies, higher educational level is a protective factor against depression. Contrary of other studies, no association is found between depression and other sociodemographic and medial factors.

Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen.

A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma.

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.

Age at natural menopause in a sample of Puerto Rican women

OBJECTIVES: To characterize the distribution of age at menopause in a sample of Puerto Rican women and to evaluate the differences in demographic, health and lifestyle factors associated with menopausal state. BACKGROUND: Age at natural menopause may be an important marker of a woman's long-term risk of chronic disease. Understanding which factors influence the timing of menopause remains limited and while ethnic differences in age at menopause have been reported, little data are available for Puerto Rican women. METHODS: In 2000, a self-administered questionnaire was completed by a sample of 300 women aged 30-59 attending health fairs in the cities of Carolina, Aguadilla and Yauco, Puerto Rico (PR). Data from this interview was used to determine age at menopause which was described with probit analysis. Women from different menopausal status groups were compared with respect to demographic, lifestyle and health characteristics by using contingency table analysis and chi-square statistics. RESULTS: In a sample where 53% of women were menopausal, the median age of natural menopause was 51.4 years (95% confidence intervals 50.3-52.5). Compared to premenopausal women, naturally and surgically postmenopausal women had lower educational attainment, increased parity and were more likely to be obese (p < 0.05). CONCLUSION: This analysis provides the first estimate of age at natural menopause among women living in PR and the age is similar to that reported in other populations. Determining whether this population tends to have an early or late menopause will facilitate a better understanding of the potential chronic disease profile of Puerto Rican women as they age.

Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement.

BACKGROUND: The aim of this study was to explore the association between extent of cutaneous involvement, presenting features and progression-free survival (PFS) in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive histology. METHODS: Previously untreated patients with localized or extensive PCNHL of aggressive histology, treated with combination chemotherapy, but excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were reviewed retrospectively. RESULTS: We identified 53 patients, of whom 52 (35 males, 17 females) were treated with doxorubicin-based regimens. Median age was 52 years (range 25-81 years), and disease was localized and extensive in 37 and 16 patients, respectively. Twenty-four patients had diffuse large B-cell lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO classification). With a median follow-up of 101 months (range 2-237 months) for survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P = 0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P = 0.002), but not extent of skin involvement, were associated with inferior PFS. Multivariate analysis revealed that only PTCL and high serum lactate dehydrogenase (LDH) were independently associated with inferior PFS. CONCLUSIONS: PTCL and elevated serum LDH level, but not extent of cutaneous involvement are associated with inferior PFS in aggressive PCNHL treated with combination chemotherapy.

Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of activity in a phase II trial.

Because irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity, we investigated its activity in relapsed or refractory non-Hodgkin's lymphomas (NHLs). Irinotecan at 300 mg/m2 i.v. was administered every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 44 registered patients, 32 are evaluable for response. Seventeen patients had received one previous regimen, and 15 patients had received two. Disease was refractory to the regimen preceding irinotecan in 12 patients. At baseline, serum lactate dehydrogenase levels were high in 47% (14/30), and beta-2-microglobulin levels were higher than 3.0 mg/L in 29% (8/28) of patients. Responses were seen in 12 of 32 (38%) patients (95% confidence interval [CI] = 21%-56%). Response rates were 43% for seven indolent (95% CI = 10%-82%), 0% for three mantle cell (95% CI = 0%-71%), 44% for 18 relapsed aggressive (95% CI = 22%-69%), and 20% for five refractory aggressive NHLs (95% CI = 1%-72%). Grade 3/4 toxicities included myelosuppression, neutropenic fever, and diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive or indolent NHL. Accrual to this study is continuing for better determination of response rates in all histologic subtypes of NHL.

Trimetrexate in relapsed T-cell lymphoma with skin involvement.

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m(2)) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/microL after 4%, and platelets less than 10,000/microL after 3% of TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.