Publications by authors named "Fernando Cabanillas"

102 Publications

Single-Arm, Open-Label Phase 2 Trial of Preemptive Methylprednisolone to Avert Progression to Respiratory Failure in High-Risk Patients with COVID-19.

medRxiv 2021 Mar 9. Epub 2021 Mar 9.

Introduction: Covid-19 is a triphasic disorder first typified by a viral phase that lasts from the first onset of symptoms until seven days later. This is followed by a second and third phase, initially characterized by the appearance of lung infiltrates, followed in 20% by respiratory failure. The second phase is usually heralded by an elevation of serologic inflammatory markers including CRP, ferritin, IL-6, LDH as well as D-dimers. Approximately 20% proceed to the second phase and are usually then treated with dexamethasone, provided they are oxygen-dependent since these are the only cases that benefit from dexamethasone. If we had objective criteria to predict this 20% that develop severe illness, they could preemptively be treated with steroids. In this exploratory study we investigated the early use of preemptive steroids in the setting of early disease, in high-risk non-oxygen dependent cases.

Methods: Eligible patients were those 21 years or older with a diagnosis of Covid-19 and oxygen saturation ≥91%. For patients to be classified as high-risk, they had to exhibit two or more of the following abnormalities 7-10 days after first symptom: IL-6 ≥ 10 pg/ml, ferritin > 500 ng/ml, D-dimer > 1 mg/L (1,000 ng/ml), CRP > 10 mg/dL (100 mg/L), LDH above normal range lymphopenia (absolute lymphocyte count <1,000 /µL), oxygen saturation between 91-94%, or CT chest with evidence of ground glass infiltrates. Primary endpoint was progression to respiratory failure. CALL score method was used to predict the expected number of cases of respiratory failure. High risk patients received methylprednisolone (MPS) 80 mg IV daily x 5 days starting no earlier than seven days from first onset of symptoms. The primary endpoint was progression to hypoxemic respiratory failure defined as PaO2 <60 mm Hg or oxygen saturation ≤90%. Secondary endpoints included survival at 28 days from registration, admission to intensive care and live discharge from the hospital. Change in levels of inflammatory markers and length of hospitalization were also assessed.

Results: In 76 patients, the expected number with respiratory failure was 30 (39.5%), yet only 4 (5.3%) developed that complication (p=.00001). Survival at 28 days was 98.6%.Improvement in inflammatory markers correlated with favorable outcome.

Conclusions: Our results are encouraging and suggest that this approach is both effective and safe.
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http://dx.doi.org/10.1101/2021.03.08.21253117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987043PMC
March 2021

Home-based management of COVID-19 by identification of low-risk features.

medRxiv 2021 Mar 26. Epub 2021 Mar 26.

Auxilio Mutuo Hospital.

Background: Covid-19 is a triphasic disorder characterized by a viral phase lasting 7-10 days from first onset of symptoms. In approximately 20% it is followed by a second stage heralded by elevation of pro-inflammatory markers such as ferritin, IL-6, CRP, LDH and D-dimers. We hypothesized that those with few abnormalities would have a low risk for progression to respiratory insufficiency and could be monitored at home without treatment.

Methods: Inclusion criteria included age >21, O saturation >90%. To be observed without treatment patients could not have >1 of the following: CRP > 10 mg/dL, high LDH, ferritin > 500 ng/ml, D-dimer > 1 mg/L, IL-6 > 10 pg/ml, absolute lymphocyte count <1,000, O sat <94%, or CT chest evidence of pneumonia. Primary endpoint: progression to respiratory failure. Secondary endpoint: 28-day survival.

Results: Of 208 entered, 132 were monitored without therapy. None progressed to respiratory failure or died.

Conclusions: We have shown that our approach can identify cases who can safely be observed without treatment, thus avoiding expensive, potentially toxic therapies, and circumventing unnecessary, costly hospitalizations. These results support our hypothesis that after applying our criteria, 64% of Covid-19 cases can be monitored as outpatients without therapy.
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http://dx.doi.org/10.1101/2021.01.25.21249684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852248PMC
March 2021

Prevalence of Complementary/Alternative Medicine use in Cancer Patients in a Tertiary Hospital in Puerto Rico.

P R Health Sci J 2020 12;39(4):294-299

Oncology Fellow at University of Puerto Rico Medical Science Campus, San Juan, Puerto Rico.

Objective: We conducted a study in a tertiary hospital to investigate complementary and alternative medicine (CAM) prevalence in a Puerto Rican population. The study also evaluated demographic and clinical factors in order to correlate them with CAM use.

Methods: Spanish speaking residents with a known diagnosis of cancer being followed in the outpatient facilities at Auxilio Mutuo Cancer Center were invited to participate in the study. Patients who read and signed a consent form were given a questionnaire inquiring, among various things, on their use of any CAM treatment, education level, gender, place of residence and whether they had consulted their oncologist. The questionnaire also asked about their expectations for use of CAM.

Results: 215 patients were approached to participate out of which 200 signed the consent and accepted to participate. A total of 95 of 200 patients (47.5%) mentioned that they utilized at least one CAM treatment. Six factors were then analyzed for their correlation with CAM usage and three yielded statistically significant results at p<.05: age group, education level, and area of residence. After multivariate analysis all of these three factors behaved as independent variables. Gender, tumor type and stage were not significantly associated with use of CAM.

Conclusion: Our data show that CAM use is significantly more common in those with higher education, younger age, and those living in non-metropolitan areas. Vitamin C and soursop (Graviola or guanábana) proved to be the two most common CAM treatments, respectively.
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December 2020

Gastric MALT Lymphoma with Biclonal Gammopathy and Bone Marrow Involvement Mimicking Multiple Myeloma.

P R Health Sci J 2020 09;39(3):275-277

Hematology and Oncology and Pathology & Laboratory programs, VA Caribbean Healthcare System, San Juan, PR.

Mucosa-associated lymphoid tissue (MALT) lymphomas are B-cell neoplasms that commonly affect the gastrointestinal (GI) tract, usually the stomach. In most cases, extranodal marginal zone lymphoma (ENMZL) is an indolent disease. Bone marrow involvement is common with MALT lymphoma accompanied by paraproteinemia; such involvement impels disease progression. Here, we present the case of an 82-year-old Hispanic patient with long-standing ENMZL in whom the gastric site responded to antibiotic treatment and Helicobacter pylori eradication, but the disease progressed over the years, with a biclonal gammopathy and bone marrow involvement with marked plasmacytic differentiation. In view of this, we suggest the routine evaluation of paraprotein in patients with ENMZL.
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September 2020

Evaluation of the MD Anderson tumor score for diffuse large B-cell lymphoma in the rituximab era.

Eur J Haematol 2020 May 18;104(5):400-408. Epub 2020 Feb 18.

Auxilio Mutuo Cancer Center, San Juan, Spain.

Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role.

Methods: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327).

Results: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment.

Conclusions: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.
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http://dx.doi.org/10.1111/ejh.13364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217048PMC
May 2020

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev).

Clin Lymphoma Myeloma Leuk 2019 12 17;19(12):776-783. Epub 2019 Jul 17.

Auxilio Cancer Center, Auxilio Mutuo Hospital, San Juan, Puerto Rico.

Purpose: To evaluate the impact of lenalidomide in patients with aggressive lymphoma who experienced less than complete response (CR) or as maintenance therapy after CR after gemcitabine, rituximab, and oxaliplatin salvage chemotherapy (GROC-Rev regimen).

Patients And Methods: Patients with relapsed/refractory non-Hodgkin lymphoma received up to 6 GROC-Rev courses: rituximab (375 mg/m provided intravenously) on day 1, oxaliplatin (100 mg/m provided intravenously; 2 hours), gemcitabine (provided 1250 mg/m intravenously; 30 minutes) on day 2, and pegfilgrastim (6 mg provided subcutaneously) on day 3. Patients switched to lenalidomide if they did not experience at least partial response (PR) after their second GROC-Rev course, or if they experienced less than a CR after 6 courses.

Results: In 33 patients, overall response was 61% (CR = 39%). Of 17 patients with PR who continued to 6 courses, 10 (59%) experienced CR and 7 PR as maximum response; of these 7, 1 died before receiving lenalidomide, 1 experienced CR while receiving lenalidomide (17%), and 2 experienced a further PR (33%). Of 16 with disease that failed to respond to GROC-Rev after their second course, 2 died before lenalidomide could be administered, and 2 experienced CR (14%) and 1 PR (7%) after lenalidomide. Overall survival and progression-free survival were 47% and 33% at 2 years. Grade 3/4 adverse events included neutropenia, thrombocytopenia, and/or anemia (n = 5), neutropenic infection (n = 3), urinary tract infection (n = 3), pneumonia (n = 2), cellulitis (n = 2), and seizure (n = 1). Eight went on to receive transplants.

Conclusion: GROC-Rev is an effective and well-tolerated salvage regimen consisting of chemotherapy followed by lenalidomide maintenance in patients with relapsed/refractory non-Hodgkin lymphoma. Simultaneous administration of these agents is worth exploring in future studies.
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http://dx.doi.org/10.1016/j.clml.2019.07.002DOI Listing
December 2019

Incidence and Risk Factors for Developing Herpes Zoster Among a Cohort of Patients Diagnosed With Lymphoma at a Community Cancer Center.

Clin Lymphoma Myeloma Leuk 2019 03 19;19(3):e153-e158. Epub 2018 Dec 19.

Endowed Health Services Research Center, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Background: Although most cases of herpes zoster (HZ) are self-limited, lymphoma patients are at greater risk for recurrences and more serious and atypical complications that can delay scheduled anti-lymphoma treatment or prevent its continuation.

Patients And Methods: This is a cohort study with a retrospective chart review of 415 patients diagnosed with lymphoma to determine the incidence and risk factors for developing HZ among this population. Data collected included date of diagnosis, patient's age, last follow-up or death, stage and presentation of lymphoma, treatment type, baseline laboratory tests, and comorbidities. Patients with a diagnosis of HZ at any time during their course of illness were identified. Patients were divided into various subgroups to analyze their risk of developing HZ individually. The frequencies of each categorical variable were compared with χ tests. Relative risks were calculated using 95% confidence intervals (CIs).

Results: During a median follow-up of 8.9 years, 46 cases of HZ were identified, with an overall incidence density of 11.1%. Higher rates of HZ were associated with lymphocytopenia (P = .038), presentation (P = .030), stage (P = .034), autologous stem cell transplant (P = .019), multiple courses of chemotherapy (P = .035), and fludarabine therapy (P = .002). Those who received what we labeled as 'highly immunosuppressive chemotherapy' had 2.9 times the risk to develop HZ than those who did not receive this therapy (95% CI, 1.47-5.623; P < .001).

Conclusions: Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Patients with the risk factors described here might benefit from antiviral prophylaxis against HZ.
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http://dx.doi.org/10.1016/j.clml.2018.12.001DOI Listing
March 2019

Successful Use of Bortezomib-Lenalidomide Combination as Treatment for a Patient With Plasmablastic Lymphoma.

Clin Lymphoma Myeloma Leuk 2018 07 4;18(7):e275-e277. Epub 2018 May 4.

Auxilio Mutuo Hospital Cancer Center, Hato Rey, Puerto Rico.

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http://dx.doi.org/10.1016/j.clml.2018.04.011DOI Listing
July 2018

Mantle Cell Lymphoma with t(11;22) (q13;q11.2) an indolent clinical variant?

Leuk Lymphoma 2018 10 7;59(10):2509-2511. Epub 2018 Feb 7.

a Auxilio Mutuo Hospital Cancer Center , San Juan , Puerto Rico.

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http://dx.doi.org/10.1080/10428194.2018.1427863DOI Listing
October 2018

Advances in Diagnosis and Management of Diffuse Large B-cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2017 Dec 7;17(12):783-796. Epub 2017 Nov 7.

Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types. The management of double hit lymphomas, which almost exclusively fall under the GCB category, is discussed, together with the double expresser phenotype, which is usually grouped under the non-GCB type. The role of lenalidomide and ibrutinib in the management of the non-GCB type is examined. We also discuss the front-line management of primary mediastinal large cell lymphoma using the EPOCH (etoposide, prednisolone, Oncovin [vincristine], cyclophosphamide, hydroxydaunorubicin [doxorubicin]) regimen and examine new salvage data on immune checkpoint inhibitors for this clinical subtype. The prognosis, clinical features, and management of de novo CD5+ DLBCL are discussed, and newer and promising developments in the management of primary central nervous system lymphomas are presented in detail. The most popular salvage regimens and the application of high-dose chemotherapy with stem cell transplantation are assessed in detail. Finally, data on new treatment tactics such as CART (chimeric antigen receptor T-cell) cells and promising new drugs, including blinatumomab and venetoclax, are presented.
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http://dx.doi.org/10.1016/j.clml.2017.10.007DOI Listing
December 2017

Results of Upfront Therapy for Marginal Zone Lymphoma.

Clin Lymphoma Myeloma Leuk 2017 Dec 23;17(12):879-883. Epub 2017 Sep 23.

Hospital Auxilio Mutuo Cancer Center, San Juan, Puerto Rico.

Background: Marginal zone lymphomas (MZLs) are indolent disorders composed of 3 subtypes: extranodal marginal zone lymphoma (MALT), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). Early-stage MALT is treated with radiotherapy or antibiotics, and advanced MALT and NMZL are managed with either watch and wait or chemotherapy. SMZLs are treated with splenectomy or rituximab. However, because these approaches have failed to cure patients with SMZL and NMZL, we have systematically used upfront chemotherapy for them, as well as for advanced MALT. We report the outcomes of this approach.

Patients And Methods: A total of 44 patients with MZL were identified from our database and divided into 2 groups. Group 1 (22 with early-stage MALT) patients received either radiotherapy (n = 17) or antibiotics with or without surgery (n = 5). Group 2 included 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Group 2 was treated with FND-R (fludarabine 25 mg/m on days 1 to 3, mitoxantrone 10 mg/m on day 1, dexamethasone 20 mg on days 1 to 5, and rituximab 375 mg/m on day 1; n = 14) or CHOP-R (cyclophosphamide 750 mg/m on day 1, doxorubicin 50 mg/m on day 1, vincristine 2 mg intravenous push on day 1, prednisone 100 mg/m orally on days 1 to 5, rituximab 375 mg/m on day 1; n = 8), followed by maintenance rituximab for 70%.

Results: All patients achieved complete remission, and only 2 patients in group 1 had developed a relapse at 70 and 75 months. Both relapses were stage I MALT that had initially been treated with radiotherapy. Both were salvaged with FND-R and remained free of disease at 27 and 39 months after the relapse. At 10 years, the failure-free survival for the 44 patients was 80% and the overall survival was 100%. None of the patients in group 2 developed a relapse. The long-term toxicities have been acceptable.

Conclusions: The excellent responses using upfront chemotherapy for MZL suggests that this disorder is curable. Our results should be confirmed in a prospective trial.
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http://dx.doi.org/10.1016/j.clml.2017.09.014DOI Listing
December 2017

Check this checkpoint inhibitor in lymphoma.

Blood 2017 07;130(3):234-235

AUXILIO MUTUO CANCER CENTER; UNIVERSITY OF PUERTO RICO SCHOOL OF MEDICINE.

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http://dx.doi.org/10.1182/blood-2017-05-786293DOI Listing
July 2017

Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma.

Br J Haematol 2017 07 17;178(2):250-256. Epub 2017 Apr 17.

Weill Cornell Medicine, New York, NY, USA.

Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.
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http://dx.doi.org/10.1111/bjh.14667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737737PMC
July 2017

High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: Results of a randomized Study.

Br J Haematol 2017 04 24;177(2):263-270. Epub 2017 Mar 24.

Department of Lymphoma and Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance. Median ages were 54 and 55 years. The two groups were comparable with the exception of a higher percentage of females (65% vs. 43%) and baseline anaemia (23% vs. 11%) in the FND followed by rituximab group. Complete response/unconfirmed complete response rates were 89% and 93%. The most frequent grade ≥ 3 toxicity was neutropenia (86% vs. 96%). Neutropenic fever occurred in 21% and 16%. Late toxicity included myelodysplastic syndrome (n = 3) and acute myeloid leukaemia (n = 5). With 12·5 years of follow-up, no significant differences based on treatment schedule were observed. 10-year overall survival estimates were 76% and 73%. 10-year progression-free survival estimates were 52% and 51%. FND with concurrent or sequential rituximab, and IFN maintenance in indolent lymphoma demonstrated high response rates and robust survival.
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http://dx.doi.org/10.1111/bjh.14541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692PMC
April 2017

Indolent Lymphomas That Present With Clinically Aggressive Features: A Subset of Low-Grade Lymphomas With a Behavior Inconsistent With the Histologic Diagnosis.

Clin Lymphoma Myeloma Leuk 2016 10 10;16(10):550-557. Epub 2016 Aug 10.

Hospital Auxilio Mutuo, Auxilio Cancer Center, San Juan, PR.

Background: The expected presentation for low-grade lymphomas consists of disseminated lymphadenopathy with no constitutional symptomsk, and with bone marrow involvement, normal lactate dehydrogenase (LDH), low proliferative rate as determined by Ki-67, and positron emission tomography (PET) scan with low standardized uptake values (SUVs) < 14. However, it is not unusual for some cases to present with 1 or more clinically aggressive features. Because the clinical behavior of such patients has not been investigated, there are no data regarding their expected outcome.

Patients And Methods: For these cases, we use the term "clinically discordant indolent histology" (CDIH), which we define as any follicular grade 1-2, grade 3-A, or small lymphocytic lymphoma that meets at least 1 or more of the following conditions at the time of diagnosis: constitutional symptoms, LDH elevation, PET SUV > 14, unusual areas of involvement for indolent non-Hodgkin lymphoma (NHL) (bone, pleura, central nervous system, soft tissue, lung), Ki-67 > 30%, necrotic areas seen on computed tomography scan, or discrete space-occupying lesions in the liver or spleen. We have reviewed our NHL database with the objective of identifying such cases so we could compare them with those with the expected presentation of indolent NHLs.

Results: Patients with CDIH have a less favorable overall survival and failure-free survival, and a higher rate of transformation to a higher-grade histology.

Conclusions: CDIH functionally behaves as aggressive NHL despite the fact that under the microscope the lymphomas resemble typical indolent NHLs. These cases seem to fare better when treated with a regimen containing doxorubicin-rituximab.
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http://dx.doi.org/10.1016/j.clml.2016.08.011DOI Listing
October 2016

Prognostic significance of baseline peripheral absolute neutrophil, monocyte and serum β2-microglobulin level in patients with diffuse large b-cell lymphoma: a new prognostic model.

Br J Haematol 2016 Oct 22;175(2):290-299. Epub 2016 Jul 22.

Departments of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum β2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum β2-microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum β2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum β2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.
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http://dx.doi.org/10.1111/bjh.14237DOI Listing
October 2016

POEMS Syndrome: A Rare Disease With A Challenging Diagnosis.

Bol Asoc Med P R 2015 Jul-Sep;107(3):85-8

A complex conglomerate of symptoms, signs, and abnormalities are present with POEMS syndrome, making the diagnosis, management and follow-up a challenge. Recognizing the disease early on may be difficult. Many patients are initially misdiagnosed as having others disorders, for example: multiple myeloma. There is no standard treatment for patients diagnosed with POEMS syndrome.
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February 2016

Metastatic Ovarian Tumor Masquerading as Atypical Pneumonia.

Bol Asoc Med P R 2015 Jul-Sep;107(3):38-41

Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal tract and a metastatic signet ring cell adenocarcinoma to the ovary. Stomach is the most common primary site, but other organs can serve as a primary site. The lymphatic system is the most likely route for metastasis. CA 125 levels can be used for screening for early detection of ovarian metastasis as well as for monitoring the course of disease. The prognosis of Krukenberg tumor is poor and no curative treatment is currently available.
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February 2016

Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center.

Br J Haematol 2016 Jan 9;172(1):80-8. Epub 2015 Dec 9.

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years).
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http://dx.doi.org/10.1111/bjh.13796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471614PMC
January 2016

Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma.

Br J Haematol 2014 Sep 9;166(6):920-8. Epub 2014 Jul 9.

Mary Babb Randolph Cancer Center, West Virginia University Robert C Byrd Health Science Center, Morgantown, WV, USA.

This non-comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab-chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21-d cycles of: bortezomib 1·6 mg/m(2) (days 1, 8), rituximab 375 mg/m(2) (day 1), cyclophosphamide 1000 mg/m(2) (day 1) and prednisone 100 mg (days 1-5; VR-CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR-CP, cyclophosphamide 750 mg/m(2) and doxorubicin 50 mg/m(2) (day 1; VR-CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR-CP, the response rate was 77%, with a 27% complete response rate. After a median follow-up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression-free survival was 21·9 and 14·9 months, respectively. Common drug-related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR-CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug-related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR-CP was active and well tolerated in patients with relapsed/refractory FL.
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http://dx.doi.org/10.1111/bjh.12991DOI Listing
September 2014

Clinical and pathological features of colorectal cancer in patients at a community hospital in Puerto Rico.

P R Health Sci J 2014 Jun;33(2):65-70

Objective: Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico.

Methods: Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age.

Results: Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival.

Conclusion: This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.
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June 2014

Recent advances in the management of mantle cell lymphoma.

Curr Opin Oncol 2013 Nov;25(6):716-21

aAuxilio Cancer Center bUniversity of Puerto Rico, School of Medicine, San Juan, Puerto Rico cUniversity of Texas, M. D. Anderson Cancer Center, Houston, Texas dUniversity of South Florida, Moffitt Cancer Center Tampa, Florida, USA.

Purpose Of Review: This review will discuss the most recent literature regarding frontline therapy, treatment of patients not eligible for intensive chemotherapy, and novel agents for relapsed/refractory patients with mantle cell lymphoma (MCL).

Recent Findings: Longer follow-up of previously studied intensive regimens still demonstrates encouraging results, but late relapses are still evident. Consolidation and maintenance strategies continue to be attractive options to be explored in this disease that is characterized by frequent relapses and short remissions. The combination of bendamustine-rituximab was demonstrated to be noninferior and less toxic to R-CHOP and should be considered the new standard of care for elderly patients. Multiple novel agents directed towards different molecular targets like BTK, mTOR, PI3K, HDAC, and BCL-2, involved in the pathogenesis of MCL have shown promising results.

Summary: Management of MCL still represents a challenge due to heterogeneity of the disease. As we approach the molecular era of oncology, future strategies should focus on combination of newer agents with known effective regimens to improve outcome.
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http://dx.doi.org/10.1097/CCO.0000000000000010DOI Listing
November 2013

Breast cancer molecular subtypes and survival in a hospital-based sample in Puerto Rico.

Cancer Med 2013 Jun 18;2(3):343-50. Epub 2013 Apr 18.

Cancer Control and Population Sciences Program, University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00927, USA.

Information on the impact of hormone receptor status subtypes in breast cancer (BC) prognosis is still limited for Hispanics. We aimed to evaluate the association of BC molecular subtypes and other clinical factors with survival in a hospital-based female population of BC cases in Puerto Rico. We analyzed 663 cases of invasive BC diagnosed between 2002 and 2005. Information on HER-2/neu (HER-2) overexpression, estrogen (ER), and progesterone (PR) receptor status and clinical characteristics were retrieved from hospitals cancer registries and record review. Survival probabilities by covariates of interest were described using the Kaplan-Meier estimators. Cox proportional hazards models were employed to assess factors associated with risk of BC death. Overall, 17.3% of BC cases were triple-negative (TN), 61.8% were Luminal-A, 13.3% were Luminal-B, and 7.5% were HER-2 overexpressed. In the multivariate Cox model, among patients with localized stage, women with TN BC had higher risk of death (adjusted hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.29-5.12) as compared to those with Luminal-A status, after adjusting for age at diagnosis. In addition, among women with regional/distant stage at diagnosis, those with TN BC (HR: 5.48, 95% CI: 2.63-11.47) and those HER-2+, including HER-2 overexpressed and Luminal-B, (HR: 2.73, 95% CI:1.30-5.75) had a higher mortality. This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression subtypes in BC survival in Puerto Rico. Consistent to results in other populations, the TN subtype and HER-2+ tumors were associated with decreased survival.
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http://dx.doi.org/10.1002/cam4.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699846PMC
June 2013

Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas.

Br J Haematol 2013 Sep 27;162(5):631-8. Epub 2013 Jun 27.

University of Texas M. D. Anderson Cancer Center (UTMDACC), Houston, TX 77030, USA.

Vincristine sulfate liposome injection (VSLI; Marqibo(®) ; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.
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http://dx.doi.org/10.1111/bjh.12446DOI Listing
September 2013

Reply to I.E. Haines.

J Clin Oncol 2013 May;31(14):1798

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http://dx.doi.org/10.1200/JCO.2013.49.4468DOI Listing
May 2013

Curability of advanced indolent or low-grade follicular lymphomas: time for a new paradigm?

J Clin Oncol 2013 Jan 8;31(1):14-6. Epub 2012 Oct 8.

Auxilio Mutuo Cancer Center, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

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http://dx.doi.org/10.1200/JCO.2012.41.7527DOI Listing
January 2013

Rectal adenocarcinoma: proposal for a model based on pretreatment prognostic factors.

P R Health Sci J 2012 Jun;31(2):52-8

University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Objective: Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aimed to determine pre-treatment prognostic factors that are associated with an unfavorable outcome.

Methods: A retrospective review of 99 rectal cancer patients operated at the Auxilio Mutuo Hospital, San Juan, Puerto Rico, and the San Pablo Hospital, Bayamón, Puerto Rico was done. Socio-demographic, clinical and treatment data were collected.

Results: Of the 99 cases, 54% were males. The mean age +/- standard deviation was 62.2 +/- 10.4. In age-adjusted Cox model, male gender (HR [95%CI]: 3.32 [1.09-10.13]), mucinous carcinoma (HR [95% CI]: 3.67 [1.25-10.77]), and clinical stages II & III (HR [95%CI]: 8.19 [1.08-62.08]) were predictors of poor prognosis. In the multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients (HR: 2.60), carcinoembryonic antigen level > or =5 ng/ml (HR: 2.55), mucinous carcinoma (HR: 2.96), and clinical stages II & III (HR: 4.96), although results were not statistically significant (p > 0.05).

Conclusion: Although current therapeutic results are relatively favorable with preoperative 5-fluorouracil and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481993PMC
June 2012

Triple negative breast cancer: a retrospective study of Hispanics residing in Puerto Rico.

P R Health Sci J 2012 Jun;31(2):45-51

University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Objective: Triple-negative breast cancer (TNBC) demonstrates unique clinicopathological characteristics and survival outcomes. Several studies have documented important disparities in Hispanic women compared to other racial/ethnic groups; nevertheless, data on this entity in a population based Latin country are very limited. Our goal was to assess demographic and clinicopathological characteristics in essentially a pure population of Puerto Rican females with TNBC residing in Puerto Rico, as well as to determine their overall survival and progression-free survival in order to compare with published data.

Methods: By searching the electronic medical records data base, 54 patients were identified as TNBC. The median follow-up period was 25 months (range, 2-78). Univariate analysis of pretreatment risk factors was conducted.

Results: The median age at diagnosis was 55 years. Of 54 cases, 51 had stage I-III presentation. T1/T2 tumors were found in 88.9% and absence of nodal involvement in 68.5%. Prognostic factors for progression free survival (PFS) that were statistically significant were lymph node involvement (p = 0.02), tumor size > 2 cm (p = 0.037) and stage IV (p = 0.00002). The 5-year overall survival and PFS were 81% and 80%, respectively.

Conclusion: RESULTS are very similar to published data on females from North America and Europe. Differences in clinical outcome and stage at diagnosis in Hispanic women with TNBC are more likely explained by socioeconomic status and adequate access to care, rather than biological/genetic differences. The association of triple-negative breast cancer with poor prognosis deserves re-evaluation given that patients with negative node involvement and no metastasis appear to be highly
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June 2012

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial.

Lancet Oncol 2012 Jul 6;13(7):716-23. Epub 2012 Jun 6.

Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Background: The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL.

Methods: Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1-21 of each 28-day cycle. 375 mg/m(2) intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632.

Findings: 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3-4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response.

Interpretation: Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL.

Funding: Celgene.
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http://dx.doi.org/10.1016/S1470-2045(12)70200-0DOI Listing
July 2012
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