Clinical nutrition as part of the treatment pathway of pancreatic cancer patients: an expert consensus.

PURPOSE: Malnutrition is a common problem among pancreatic cancer (PC) patients that negatively impacts on their quality of life (QoL) and clinical outcomes. The main objective of this consensus is to address the role of Medical Nutrition Therapy (MNT) into the comprehensive therapeutic management of PC patients. METHODS: A Spanish multidisciplinary group of specialists from the areas of Medical Oncology; Radiation Oncology; Endocrinology and Nutrition; and General Surgery agreed to assess the role of MNT as part of the best therapeutic management of PC patients. RESULTS: The panel established different recommendations focused on nutritional screening and nutritional screening tools, MNT strategies according to PC status, and MNT in palliative treatment. CONCLUSIONS: There is an unmet need to integrate nutritional therapy as a crucial part of the multimodal care process in PC patients. Health authorities, health care professionals, cancer patients, and their families should be aware of the relevance of nutritional status and MNT on clinical outcomes and QoL of PC patients.

Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer.

Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15-20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC.

Aldehyde dehydrogenase isoform 1 (ALDH1) expression as a predictor of radiosensitivity in laryngeal cancer.

BACKGROUND: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. METHODS: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. RESULTS: ALDH1 expression was detected in 17.5 % (10/57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1-. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 + group versus 48.9 % for ALDH1- patients (p = 0.034). CONCLUSION: The patients in this study with ALDH1 + tumours had better outcomes than their counterparts with ALDH1- tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed.

Estudio Cualitativo: uso de la guía para la estimación del riesgo cardiovascular global en la práctica clínica / Pesquisa Qualitativa: Uso Dos Guias Para A Estimativa De Risco Cardiovascular Global Na Prá- Tica Clínica / Qualitative Study: The Use Of The Guidelines For The Assessment Of Absolute Cardiovascular Disease Risk In Clinical Pracice

El Ministerio de Salud, a través del Programa Remediar y con la participación de 24 Facultades de Medicina, implementa un Programa de Capacitación en Terapéutica Racional de Atención Primaria de la Salud (TRAPS) destinado a médicos/as que se desempeñan en el primer nivel de atención (PNA). En el Curso sobre Riesgo Cardiovascular Global (RCVG) se promueve la utilización de la Guía de la OMS adaptada para Argentina para la estimación del riesgo. Objetivo. Presentar los resultados de un estudio cualitativo que indaga, entre los profesionales que habían asistido al curso, el conocimiento y la utilización de la Guía. Material y Método. Población: médicos/as que se desempeñan en Centros de Salud en las provincias de Catamarca y La Rioja...

The Ministry of Health, through a Program called “Remediar” and with the participationof 24 Schools of Medicine, is implementing a Training Program on Rational Therapeuticsin Primary Health Care intended for doctors working in the fi rst level of care. In theCourse on Absolute Cardiovascular Disease Risk (ACVDR), the use of WHO Guidelinesfor the Assessment of Risk adapted for Argentina is promoted.Objective: To present the results of a qualitative study enquiring professionals who attendedthe course, regarding the knowledge and use of the Guidelines.Material and Method: Semi-structured deep interviews to explore dimensions such as patient-doctorrelationship, the approach to people with cardiovascular disease risk and thefactors involved in the process of patient care.Population: Doctors who work in Health Centers in the provinces of Catamarca and LaRioja and took the course on ACVDR.Results: Interviews took place between...

O Ministério da Saúde, por meio do Programa “Remediar” e com a participação de 24Faculdades de Medicina, implementa um Programa de Treinamento sobre Terapêutica Racionalde CuIdados Primários da Saúde (TRAPS) para médicos as que servem no primeiro nível de cuidados (PNA). No curso sobre Risco Cardiovascular Global (RCVG) é promovidaa utilização do Guia da OMS adaptado para a Argentina para a estimativa de risco.Escopo: Apresentar os resultados de um estudo qualitativo que questiona, entre os profi ssionaisque participaram do curso, sobre o conhecimento e o uso do Guia.Material e métodos: Entrevistas em profundidade semi-estruturadas, através das quais sãopesquisadas as dimensões, tais como relação médico-paciente, a abordagem de pessoascom risco cardiovascular e dos fatores institucionais envolvidos no processo dos cuidadosPopulação: Médicos que trabalham em centros de saúde nas províncias de Catamarca e LaRioja, e que fi zeram o curso em RCVG...

Role of 3.0 T multiparametric MRI in local staging in prostate cancer and clinical implications for radiation oncology.

PURPOSE: To evaluate the accuracy of preoperative 3T multiparametric magnetic resonance imaging (3TmMRI) for local staging of prostate cancer and its influence on the decision to change the clinical target volume (CTV), total dose and hormonal therapy when treating prostate cancer patients with radiotherapy. METHODS: From 2009 to 2013, 150 patients, who had confirmed prostate cancer and underwent a 3TmMRI before treatment with radical prostatectomy or radical radiation therapy, were included. Radiation therapy treatment (CTV, total dose and hormonal therapy) was initially determined on the basis of the clinical information, and radiation therapy plan was reevaluated after 3TmMRI review. The value of preoperative 3TmMRI in local staging and in the decision of radiotherapy treatment according to NCCN risk classification was analyzed. RESULTS: 3TmMRI performed correct, over- and under staging in 78.7 % (37/47), 6.3 % (3/47), 14.8 % patients (7/47), respectively. 3TmMRI identified 6 cT2a, 7 cT2b, 28 cT2c, 3 cT3a, 3 cT3b tumors. At final pathology, 5 tumors were classified as pT2a, 5 as pT2b, 30 as pT2c, 4 as pT3a, 3 as pT3b. After reviewing the MRI reports, the initial radiotherapy and hormonal therapy plan was changed in 33.9 % patients (35/103). CONCLUSIONS: In our group of patients, 3TmMRI has been a reliable technique providing an optimal staging for prostate cancer. Its routine use could induce important changes in radiation therapy treatments in a significant number of such patients. However, more additional studies are needed to clarify this issue.

Oropharyngeal cancer related to Human Papilloma Virus: incidence and prognosis in Madrid, Spain.

PURPOSE: To report the incidence of HPV-related oropharyngeal cancer (OC) in our region, and determine the influence of HPV status on survival among patients treated with chemoradiation (CRT). METHODS: A total of 102 patients with stage II-IV OC treated by CRT at four hospitals in Madrid, Spain were retrospectively reviewed. Immunohistochemistry analysis was performed to evaluate p16 expression in pretreatment tumor block samples obtained from these patients. HPV-positive and HPV-negative patients were compared to assess differences in overall survival (OS), loco-regional control and disease-free survival. RESULTS: Of the tumor samples evaluated, 26.7 % were p16 positive. HPV-positive patients were younger (median age, 56 vs 59 years; p = 0.052). No significant differences were observed in terms of tumor stage, gender, or smoking habit between HPV+ and HPV- patients. HPV+ patients showed a trend towards better OS (67.4, vs 49.7 %; hazard ratio, 0.55; p = 0.095). CONCLUSIONS: Incidence of HPV-related OC in our region is similar to that reported in other regions in Europe, yet lower than in North America. We observed a trend for improved OS in patients with HPV+ oropharyngeal cancer.

Uso racional de medicamentos: Evaluación de un curso de capacitación / Uso racional de medicamentos: avaliação de um curso de formação / Rational use of drugs: assessment of a training course

El Programa Remediar del Ministerio de Salud de la Naciónimplementó, entre 2006 y 2008 un Curso en Uso Racionalde Medicamentos destinado a médicos y odontólogos quese desempeñaban en los Centros de Atención Primaria dela Salud que recibían el botiquín con los medicamentosdel Programa Remediar. El Curso tenía como propósitogeneral promover el uso racional de medicamentos entrelos profesionales prescriptores del primer nivel de atención.Se establecieron acuerdos entre el Ministerio de Salud de laNación (MSAL), los Ministerios de Salud Provinciales y 23Facultades de Medicina. La política del MSAL fue involucrara la comunidad académica en un trabajo conjunto orientadoa jerarquizar la Atención Primaria de la Salud (APS). Elcurso se dictó para tres cohortes, en total 4463 profesionalesiniciaron el curso y 2776 lo completaron aprobando unexamen final. Funcionaron 118 sedes-aulas; participarontodas las jurisdicciones del país. El curso URM fue evaluadopor el Área de Monitoreo y Evaluación del Remediar usandolos registros de datos administrativos sobre rendimientoacadémico por provincia y realizando 15 grupos focales endistintas localidades. El objetivo del presente artículo es dara conocer la metodología utilizada y los resultados obtenidos en la Evaluación del Curso URM con el propósito de hacer un a contribución para elmejoramiento de futuras intervenciones.

Remediar Program of the National Ministry of Health implemented between 2006 and 2008Rational Use of Drugs’ Courses for doctors and dentists who worked in the Primary CareCenters Health receiving the kit with medicines from Remediar. The training was intendedgenerally to promote rational use of medicines for professional primary care prescribers.Agreements were established between the National Health Ministry, Provincial HealthMinistries and 23 medical schools. The Health Ministry policy was to involve the academiccommunity in a joint effort aimed at prioritizing the Primary Health Care. The course washeld for three cohorts, totaling 4463 professional, 2776 started the course and completed itby passing a final exam. They ran 118 seats of classrooms, involving all jurisdictions. URMCourse was evaluated by the Monitoring and Evaluation Area using administrative data onacademic performance by province and conducting 15 focus groups in different locations.The aim of this paper is to present the methodology used and the results obtained in theURM Course Evaluation in order to make a contribution to improve future interventions.

Polymorphisms in HIF-1alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx.

BACKGROUND: HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. METHODS: We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. RESULTS: Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). CONCLUSIONS: The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size.

Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis.

Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF-21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA.

Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Serum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH. RESULTS: The levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1. CONCLUSION: These observations indicate that DKK-1 may play a significant role in bone formation during DISH.

[Radiotherapy in dermatology]. / Radioterapia en Dermatología.

Ionizing radiation causes cell death through DNA damage and has a stronger effect on undifferentiated tumor cells with a high mitotic rate. The use of a fractionated radiotherapy regimen improves both efficacy and tolerance. In addition, greater fractionation, with lower doses per session, minimizes adverse effects. In the majority of tumors treated with radical radiotherapy, the tumor cells do not disappear immediately after treatment, and assessment of the final response to treatment before three months is premature. Radiotherapy is an important treatment modality in selected patients with skin cancer. Modern radiotherapy equipment and techniques achieve excellent rates of tumor control, associated with good cosmetic results, preserved function, and a low rate of complications. The choice of technique is determined by tumor size and site and the thickness. The techniques most widely used at the present time include external beam radiotherapy with linear accelerators and high-dose-rate brachytherapy.

Invasive bladder cancer: a single-institution experience with bladder-sparing approach.

Our objective was to assess the efficacy and safety of a selective bladder-preserving approach by transurethral resection and sequential chemoradiotherapy in patients with muscle-invasive bladder cancer. From 1989 through 1997, 40 patients with biopsy-confirmed bladder cancer, clinical stages T2-4NxM0, were treated with induction by aggressive transurethral resection (TUR) and three cycles of methotrexate, cisplatin, and vinblastine (MCV) chemotherapy. Tumor response was evaluated by cystoscopy and biopsy. In complete responders, the treatment was continued by radiotherapy (60 Gy to the bladder and 50 Gy to pelvic lymph nodes). Radical cystectomy was recommended to patients with residual tumor. Clinical complete response rate to TUR and MCV chemotherapy was 70%. The 4-year actuarial overall survival rate for the whole series was 80.5%. Among 36 patients who completed chemotherapy and radiotherapy, the 4-year actuarial survival was 84%, with 82.6% surviving with their bladders intact. Freedom from local failure in complete responders to TUR-chemotherapy was 84%. Multivariate analysis revealed that the extent of initial TUR and status after TUR-chemotherapy were independent prognostic factors associated with survival and disease-free survival. This study confirms that the combination of aggressive TUR and sequential chemoradiotherapy with bladder preservation is an alternative treatment option to primary cystectomy for selected patients with invasive bladder carcinoma.

Primary lymphoma of brain: results of management of a modern cohort with radiation therapy.

PURPOSE: To assess the outcome and prognostic factors for patients with primary lymphoma of brain managed with radiation therapy between 1979 and 1988. METHODS AND MATERIALS: A retrospective review was undertaken of 49 patients referred to Princess Margaret Hospital. There were 25 males and 24 females. Median age was 60 years, with a range of 17-80 years. Tumors were located supratentorially in 35, infratentorially in 10, and both in 4 patients. Single masses were demonstrated on CT brain in 36, and multiple lesions in 13 patients. Cranial irradiation was given in 48, and 11 patients received chemotherapy. All patients in this series were immunocompetent. RESULTS: Over a follow-up range of 3-11 years of surviving patients, with a median of 6 years, 40/49 patients have died. Overall median survival was 1.4 years (17 months) and 5-year actuarial survival was 26%. Statistical analysis revealed the following significant factors: Karnofsky performance status (KPS), age, and distribution pattern of disease on presenting CT brain. Five-year actuarial survival for patients with a KPS > 60 or <60 was 56% and 10%, respectively (P = 0.01); for patients with age < 60 or >60, 5-year actuarial survival was 42% and 9%, respectively (P = 0.03); for patients with solitary or multiple lesions, 5-year actuarial survival was 30% and 15%, respectively (P = 0.04). CONCLUSIONS: We conclude that Karnofsky performance status, age, and distribution pattern on pretreatment CT of brain are significant prognostic factors in primary lymphoma of brain, and that new approaches need to be developed for these patients.

Successful bone marrow transplantation in sensitized aplastic anemia patients using total lymphoid irradiation for conditioning: long-term follow-up.

Between June 1986 and November 1994, 22 previously transfused patients with severe aplastic anemia (SAA) were treated with high-dose cyclophosphamide (CY) (50 mg/kg over 4 consecutive days) and 7 Gy total lymphoid irradiation (TLI) in two fractions before allogeneic bone marrow transplantation (BMT) from HLA-identical sibling. Graft-versus-host-disease (GVHD) prophylaxis included the combination of methotrexate and cyclosporine A in all cases. Actuarial survival at 5 years is 73 +/- 9 per cent for the entire group and 86 +/- 13 per cent for the seven patients < or = 18 years. The incidence of graft failure was 0 per cent, and of acute GVHD and chronic GVHD was 31.5 per cent and 24 per cent respectively. Prolonged interval from diagnosis to BMT adversely influenced survival (P = 0.03). No hypothyroidism or secondary malignancies have been documented in this series. Our findings indicate that survival with CY-TLI is comparable to that obtained using preparative regimens without radiation. The changing role of radiotherapy in pretransplant immunosuppression for SAA is discussed.

Prognostic factors affecting leukemia relapse after allogeneic BMT conditioned with cyclophosphamide and fractionated TBI.

Between June 1985 and May 1992, 94 consecutive patients with acute myeloid leukemia (AML = 28), acute lymphoblastic leukemia (ALL = 27) and chronic myelogenous leukemia (CML = 39), were transplanted using genotypically HLA-identical marrow donors. All were conditioned with cyclophosphamide (CY) plus 12 Gy fractionated TBI. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A alone in nine patients and methotrexate-cyclosporin A in 85 patients. Forty-eight patients developed grades II-IV acute GVHD and 24 of 68 patients who survived at least 100 days developed chronic GVHD. The 5-year actuarial probability of survival, event-free survival and relapse were 41 +/- 5%, 37 +/- 5% and 37 +/- 6%, respectively. In multivariate analysis, an increased risk of leukemia relapse was associated with (1) absence of chronic GVHD (P = 0.017), (2) advanced disease at transplant (P = 0.034) and (3) diagnosis of AML (P = 0.047). Our results confirm that disease status at transplant and chronic GVHD are the more important risk factors associated with leukemia relapse, and suggest that CY-TBI has only a partial role in eradicating leukemia in AML.

The lymph node pathology of Omenn's syndrome.

Omenn's syndrome is a rare, usually fatal immunologic disorder of infancy characterized by recurrent infections, skin lesion, lymphadenopathy, peripheral blood lymphocytosis, and eosinophilia. Histologic evaluation of a lymph node revealed total effacement of the microscopic architecture resulting from a diffuse proliferation of interdigitating reticulum cells and a depletion of B lymphocytes. The lymph node lacked a distinct cortex and had no follicle formation. The most striking feature was a diffuse hyperplasia of S-100-protein-positive nonphagocytic reticulum cells with large, pale Langerhans-like nuclei. Ultrastructural examination identified these cells to be interdigitating reticulum cells. The lymphocytes were small and predominantly of the CD8 cytotoxic/suppressor cell type.

[A comparative study in rectal adenocarcinoma: preoperative or postoperative radiotherapy]. / Estudio comparativo en el adenocarcinoma de recto: radioterapia preoperatoria o postoperatoria.

PURPOSE: To compare the results of preoperative and postoperative radiotherapy in rectal adenocarcinoma, in terms of overall survival and disease-free survival. PATIENTS AND METHODS: From 1989 to 1993, 52 patients with clinically operable rectal cancer were retrospectively analyzed. Two groups were compared: Patients in Group I received postoperative radiotherapy and those in Group II preoperative radiotherapy. Patients with a Karfnosky index > 70%, no evidence of distant disease and no major systemic problems were included in this study. RESULTS: The overall 5-year actuarial survival was 75% in Group I and 83% in Group II. The 5-year disease-free survival was 52% in Group I compared to 86% in Group II, a statistically significant difference (p = 0.025). A reduction in all Dukes' stages was observed in the preoperative radiation group, allowing preservation of the anorectal function in an increased number of patients. CONCLUSIONS: We observed better results with preoperative radiotherapy and conclude that this treatment might be justified in rectal carcinoma.

Squamous cell carcinoma of the lip: analysis of the Princess Margaret Hospital experience.

We reviewed 117 patients with squamous cell carcinoma of the lip who were treated at the Princess Margaret Hospital between 1976 and 1985. Ninety-eight cancers arose from the lower lip, 18 from the upper lip and 1 from the commissure. Two patients had lymph node metastases at presentation. Sixty-one patients were treated with radiation therapy following a biopsy, 28 underwent surgery followed by post-operative radiation, and 28 had surgery alone. With a median follow-up time of 5.4 years, the 5-year actuarial overall and cause-specific survival rates were 81% and 99%, respectively. Local failure developed in 4 patients after radiation treatment, 3 of whom were salvaged by surgery. Six patients developed regional metastases after initial treatment, 4 of whom were salvaged with surgery and/or radiotherapy. Two patients died from lip cancer. After a univariate analysis, the only factor which predicted for nodal failure was T stage of the primary lesion, with a 4% risk of nodal failure for T1 lesions vs. 20% for T2/3 lesions (p = 0.03). No other patient, tumour or treatment variables influenced loco-regional control or survival in a statistically significant manner. Cosmetic and functional outcome were evaluated in 8 patients whose radiation treatments were administered 13 years ago. No patients had compromised lip function, and the majority had minimal cosmetic sequelae from their radiation therapy. Based on the excellent results of this review, we would continue to recommend radiation therapy as an effective treatment modality for patients with lip cancer because of the ease by which the entire tumour can be encompassed whilst maintaining excellent cosmetic and functional outcome.

Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. A multivariate study of 492 cases.

A multivariate analysis was carried out in 492 patients with metastatic neck disease from squamous cell carcinoma to determine the influence of clinical and therapeutic factors on survival, local and regional control, and distant metastases. After radiation treatment with radical intent, recurrence at the primary site was the most frequent site of treatment failure (20% of cases), followed by distant metastases (14% of the cases), whereas isolated neck recurrences occurred in only 7% of the patients. The most significant factors influencing survival were primary tumor site, node fixation, N-stage, T-stage, and number of lymphatic chains. The most significant factors influencing local control were primary site, T-stage, and node fixation. Significant factors influencing regional control were radiation therapy volume, primary tumor site, node fixation, and node location (upper and lower neck). Significant factors influencing distant control were N-stage, number of nodes, and number of involved lymphatic chains.

Laboratory correlates and prognostic significance of granular acute lymphoblastic leukemia in children. A Pediatric Oncology Group study.

As part of a comprehensive prospective clinicopathologic study by the Pediatric Oncology Group (POG), 2,092 children with acute lymphoblastic leukemia (ALL) were evaluated by uniform morphologic, cytochemical, and immunologic methods to assess the frequency and implications of granular lymphoblasts. All cases were Sudan black or myeloperoxidase negative and met French-American-British (FAB) morphologic criteria for ALL. Granular ALL, characterized by the presence of more than 5% marrow blasts with at least three clearly defined azurophilic cytoplasmic granules, was identified in 56 of the 1,252 fully studied cases (4.5%). The frequency of granular features did not differ among early pre-B (4.3%), pre-B (3.6%), and T (5.8%) ALL; no cases were identified among the 12 patients with B ALL. Within the early pre-B/pre-B group, granular ALL was equally distributed between good- and poor-risk clinical groups but was more frequent among FAB L2 than FAB L1 cases (12% vs. 2%; P less than or equal to 0.001). Patients were treated with standard POG protocols for early pre-B/pre-B and T ALL. Complete remission (CR) rates were significantly lower for those with granular lymphoblasts, regardless of risk group, immunophenotype, or FAB type. Analysis of event-free survival (EFS) showed a significantly poorer outcome for granular early pre-B/pre-B cases with FAB L2 morphologic characteristics (P less than 0.001) and for those classified as poor risk (P = 0.015). These findings suggest a relationship between granules and L2 morphologic characteristics in childhood ALL and indicate that the presence of granular lymphoblasts conveys a worse prognosis for certain subgroups of children with ALL.