The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation.

Development of graft-versus-host disease (GvHD) is a rare complication after transfusions or solid organ transplantation. Patients typically present with a skin rash, diarrhea, liver failure, and bone marrow aplasia. A diagnosis of transfusion/transplantation associated-GvHD is made based on the clinical and histologic evidence, yet it is often delayed due to the nonspecific symptoms attributed to the patient's underlying illness. Several therapeutic approaches are being used including both increasing and withdrawing immunosuppression, and the use of cellular therapies. Unfortunately, the success rate of these approaches is low and the mortality of this complication is very high. New approaches are needed. We report on three cases of GvHD developing after solid organ transplantation treated with ruxolitinib.

CLAUDINS 1, 3, 4, 7 AND 10-YEAR SURVIVAL IN TRIPLE-NEGATIVE BREAST TUMORS / Claudinas 1, 3, 4, 7 e sobrevida de 10 anos em tumores de mama triplo-negativos

Purpose: Breast cancer is a major cause of morbidity and mortality and is known to be a heterogeneous disease. The clinical and molecular characterization of its subtypes is critical to guide its prognosis and treatment. The study of the expression of Claudins (CLDN) might help in the characterization of these tumors. This study investigated the association of expression of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 with 10-year survival in a series of triple-negative breast cancers. Methods: Eighty triple negative tumors were analyzed by automated immunohistochemistry for CLDN-1, CLDN-3, CLDN-4 and CLDN-7. The immunohistochemical expression was assessed by the H-Score (intensity multiplied by the percentage of staining on membrane). The associations between the expression of CLDN and 10-year survival were evaluated by Kaplan-Meier curves and Cox regressions. Results: Positive expression (H-score ≥50) of CLDN-1, CLDN-3, CLDN-4 and CLDN-7 were observed in 41.3, 77.5, 67.5 and 18.8% of the cohort, respectively. Patients with positive CLDN-1 expression had a significant lower survival than their counterparts [HR=2.37 (95%CI 1.19­4.72)]. Further, CLDN-3 was inversely associated with overall survival. Patients with positive expression of CLDN-1 and negative expression of CLDN-3 had a HR 10.4 (95%CI 3.40­31.8) higher than patients with negative expression of CLDN-1 and positive expression of CLDN-3. Neither CLDN-4 nor CLDN-7 expression was associated with 10-year survival. Conclusions: Differential expression of CLDN can help in clinicopathological characterization of triple-negative tumors. Moreover, CLDN-1 and CLDN-3 appear to be important prognostic factors for these tumors.

Objetivo: O câncer de mama é uma das principais causas de morbidade e mortalidade, conhecido por ser uma doença heterogênea. A caracterização clínica e molecular de seus subtipos é fundamental para orientar seu prognóstico e tratamento. O estudo da expressão de claudinas (CLDN) pode auxiliar na caracterização desses tumores. Este estudo investigou a associação da expressão de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 com 10 anos de sobrevida em uma série de cânceres de mama triplo-negativos. Métodos: Oitenta tumores triplo-negativos foram analisados por imuno-histoquímica automatizada para CLDN-1, CLDN-3, CLDN-4 e CLDN-7. A expressão imuno-histoquímica foi avaliada pelo escore H (intensidade multiplicada pela porcentagem de coloração na membrana). As associações entre a expressão de CLDN e a sobrevida em 10 anos foram avaliadas pelas curvas de Kaplan-Meier e regressões de Cox. Resultados: Foi observada expressão positiva (escore H ≥ 50) de CLDN-1, CLDN-3, CLDN-4 e CLDN-7 em 41,3, 77,5, 67,5 e 18,8% da coorte, respectivamente. Pacientes com expressão positiva de CLDN-1 tiveram uma sobrevida significativamente menor do que suas contrapartes [HR = 2,37 (IC 95% 1,19-4,72)]. Além disso, o CLDN-3 foi inversamente associado à sobrevida global. Pacientes com expressão positiva de CLDN-1 e expressão negativa de CLDN-3 tiveram uma FC 10,4 (IC 95% 3,40­31,8) vezes maior do que pacientes com expressão negativa de CLDN-1 e expressão positiva de CLDN-3. Nem a expressão de CLDN-4 nem de CLDN-7 foi associada a uma sobrevida de 10 anos. Conclusões: A expressão diferencial de CLDN pode ajudar na caracterização clinico-patológica de tumores triplo-negativos. Além disso, CLDN-1 e CLDN-3 parecem ser importantes fatores prognósticos para esses tumores.

Expression of cancer stem cell markers in basal and penta-negative breast carcinomas--a study of a series of triple-negative tumors.

PURPOSE: Breast cancer is a heterogeneous disease. Immunohistochemistry has given rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of neoplasia and its heterogeneity has been strongly debated in cancer stem cells (CSC) theme. This study investigates the prevalence of basal (BCC) and penta-negative carcinomas (5NC) in TNC and establishes associations with CSC (CD44CD24). MATERIALS AND METHODS: 94 TNC were tested for CK5/6, HER1, CD44 and CD24, evaluated by a simple immunohistochemistry score and correlated with clinicopathological and survival data. RESULTS: BCC had higher tumor grades than 5NC (p=0.004). CD44 negativity (p=0.007) and CD44(-)CD24(+) phenotype (p=0.013) were associated with less vascular invasion amongst TNC. CD44 expression was associated with BCC (p=0.007). CD44(-)CD24(-/low) phenotype was associated with 5NC. None of the variables were associated with clinical outcome. CONCLUSION: BCC and 5NC are closely related tumor subtypes. CD44(-)CD24(-/low) phenotype was associated with 5NC and CD44(-)CD24(+) phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.

Systemic therapy in primary angiosarcoma of the spleen.

Primary splenic angiosarcoma is a very rare neoplasm with a high propensity for metastatic disease and poor prognosis. There is a paucity of literature concerning this specific sarcoma subtype and the role of systemic therapy is not well defined. A retrospective review of the prospectively maintained University of Washington/Seattle Cancer Care Alliance Sarcoma Unit database was performed to identify patients with splenic angiosarcoma treated between 2007 and 2012. In total there were 19 patients with angiosarcoma treated at the Seattle Cancer Care Alliance from 2007 to 2012. The number of patients with splenic angiosarcoma was 2 (11%). The first patient was a woman aged 57 years who was referred with metastatic splenic angiosarcoma to the liver, post-splenectomy. She was treated with 4 cycles of weekly paclitaxel prior to metastatic resection and 4 cycles of the same drug in an adjuvant scenario, achieving a pathological complete response to treatment. She is alive and on third-line systemic therapy. The second patient was a male patient aged 30 years who presented with metastatic high-grade splenic angiosarcoma and was treated with 3 lines of systemic therapy, including doxorubicin, paclitaxel and gemcitabine+docetaxel, but developed a gastrointestinal metastasis with subsequent gastrointestinal bleeding. Splenic angiosarcoma is a very rare neoplasm. Surgery remains the mainstay of management for localized disease. Paclitaxel administered weekly proved to be well-tolerated and resulted in a good radiological response in one of our patients, enabling resection of metastatic disease. Durable clinical benefit can be achieved in metastatic splenic angiosarcoma with multi modality management.