Guilherme Fleury Perini

Brentuximab Vedotin in CD30+ Lymphomas

Monoclonal antibodies (mAb) have become an effective treatment strategy for hematologic malignancies. CD30 is a rational target for therapy due to its limited expression on normal tissues and the strong and uniform expression on malignant cells in classical Hodgkin’s lymphoma (cHL) and anaplastic large-cell lymphoma (ALCL). Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, utilizes the targeting properties of mAb to deliver a cytotoxic agent inside the malignant cell. Brentuximab vedotin has significant clinical activity in patients with relapsed or refractory cHL and relapsed or refractory ALCL, and has the potential to represent a significant advance in modern oncology.

Molecular biology of Philadelphia-negative myeloproliferative neoplasms.

Myeloproliferative neoplasms are clonal diseases of hematopoietic stem cells characterized by myeloid hyperplasia and increased risk of developing acute myeloid leukemia. Myeloproliferative neoplasms are caused, as any other malignancy, by genetic defects that culminate in the neoplastic phenotype. In the past six years, since the identification of JAK2V617F, we have experienced a substantial increase in our knowledge about the genetic mechanisms involved in the genesis of myeloproliferative neoplasms. Mutations described in several genes have revealed a considerable degree of molecular homogeneity between different subtypes of myeloproliferative neoplasms. At the same time, the molecular differences between each subtype have become clearer. While mutations in several genes, such as JAK2, myeloproliferative leukemia (MPL) and LNK have been validated in functional assays or animal models as causative mutations, the roles of other recurring mutations in the development of disease, such as TET2 and ASXL1 remain to be elucidated. In this review we will examine the most prevalent recurring gene mutations found in myeloproliferative neoplasms and their molecular consequences.

Challenges and opportunities in primary CNS lymphoma: A systematic review

BACKGROUND Historically, high-dose methotrexate (HD-MTX) plus consolidation chemotherapy and/or whole brain radiotherapy (WBRT) has been the gold standard on Primary Central Nervous System Lymphoma (PCNSL) management. We sought to examine and summarize the data, on clinical trial (CT) setting, investigating multi-modality treatment to PCNSL. METHODS We performed a systematic review of electronic databases (Medline, EMBASE, Cochrane Database and clinicaltrials.gov) and a manual search to identify original PCNSL phase 2 and phase 3 CT from the last 10years. After a 4stage Prisma based selection process, 32 published (3 Randomized CT and 29 phases 2 CT) studies ultimately were selected for review. Four ongoing clinical trials found on clinicaltrial.gov were reviewed. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated each study independently. FINDINGS Treatment of PCNSL requires a multidisciplinary approach. HD-MTX represents the most accepted standard of care induction therapy for newly diagnosed PCNSL. When HD-MTX is given with WBRT for consolidation delayed neurotoxicity can be an important complication, particularly in elderly patients. Studies have suggested that WBRT may be deferred until relapse without compromising survival and deferring WBRT may be the best approach in elderly patients. Results from dose-reduced WBRT and consolidative HD-Ara-C are encouraging. High-dose chemotherapy in combination with autologous stem cell transplantation (HDC-ASCT) as chemotherapy alone has emerged as an important consolidative treatment for selected population. The optimal salvage therapy is still to be defined. CONCLUSION WBRT for consolidation is a well-studied modality; however emerging options to selected population such as HDC-ASCT, dose-reduced WBRT or chemotherapy alone are associated with similar survival outcome and less neurotoxicity in selected series. Ongoing and future clinical trials will better define the best approach on this rare disease.

Central nervous system prophylaxis in peripheral T-cell lymphoma

To the editor: The role of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL)[1][1],[2][2] and mantle cell lymphoma[3][3],[4][4] has been addressed in recent Blood issues. The role of CNS prophylaxis is still controversial, particularly after the introduction of

A life-threatening case of TAFRO syndrome with dramatic response to tocilizumab, rituximab, and pulse steroids: The first case report in Latin America

Rationale: This is the report of the first case of TAFRO syndrome (Thrombocytopenia, Anasarca, myelofibrosis, Renal dysfunction, Organomegaly) in Latin America. Patient concerns: The patient was a 61-year-old white woman of Ashkenazi Jewish descent, who presented with a history of 8 days of nausea, vomiting, and fever; severe pitting edema in both legs, ascites, splenomegaly, and palpable axillary lymph nodes. Diagnoses: Abdominal computed tomography (CT) showed bilateral pleural effusion and retroperitoneal lymph node enlargement. Interventions: Anasarca and worsening of renal function led to admission to the intensive care unit (ICU) with multiple organ failure, requiring mechanical ventilation, vasopressor medications, and continuous renal replacement therapy (CRRT). Diagnosis of TAFRO syndrome was made on day 18 after admission, based on clinical findings and results of bone marrow and lymph node biopsies. She was treated with methylprednisolone, tocilizumab, and rituximab. One week after the first tocilizumab dose, she had dramatic improvements in respiratory and hemodynamic status, and was weaned from ventilator support and vasopressor medications. Outcomes: After 2 weeks of therapy, CRRT was switched to intermittent hemodialysis. On day 46, the patient was discharged from the ICU to the general ward, and 3 months after admission, she went home. Lessons: Provided the interleukin-6 measurement is available, this approach is suggested in cases of TAFRO syndrome, in order to customize the treatment.

Primary central nervous system lymphoma: what a neurologist/neurosurgeon should know?

Primary central nervous system lymphoma is a rare disease, with bad prognosis. Neurologists and neurosurgeons should be familiar with the diagnostic,and biologic features, as well as the initial management of patients. A correct approach to these patients is mandatory for a better outcome.

Nilotinib post-liver transplantation for acute hepatic failure related to imatinib

This is the case report of a 47-year-old woman referred to our institution due to acute liver failure related to imatinib, who was submitted to a successful liver transplantation. Nilotinib was safely used post-transplant.

Alemtuzumab in the reversal of encephalopathy associated with hypereosinophilic syndrome

A 63-year-old woman who had a 1-year history of FIP1L1PDGFRa-negative hypereosinophilic syndrome, presented with the sudden onset of ataxia and strength loss in lower extremities, spatial disorientation, and neglect of the left side of her body. She had an eosinophil count of 161AE8 · 10/l. Brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery (FLAIR) sequence showed extensive bilateral and diffuse abnormalities situated in watershed regions (left panel). Therapy with corticosteroids, hydroxycarbamide, interferon-a (5 000 000 units/day), and low-dose subcutaneous cytarabine (20 mg/day) was effective in reducing her eosinophil count, which stabilized at 40 · 10/l. Neurological symptoms were also stable. Four months after this presentation, the patient was readmitted with significant worsening of her neurological symptoms, with cerebellar ataxia and urinary incontinence. The patient was treated with subcutaneous alemtuzumab at a dose of 30 mg/week. She had an excellent response, with the eosinophil count stabilizing at 5 · 10/l after three doses, achieving a partial haematological response. A 6-month MRI follow-up showed decrease in the size of the lesions (right panel).

Everolimus as a single agent in refractory or relapsed Hodgkin's lymphoma: the Brazilian Named Patient Program Experience

Background Despite all the scientific progress that has been made on understanding the disease, prognosis for patients with relapsed and refractory Hodgkins lymphoma remains poor and the treatment is palliative in the majority of the cases. Thus, the aim of this study was to present the results on the compassionate use of everolimus in a group of patients who were monitored at nine different centers in Brazil. Methods A 10-mg oral dose of everolimus was given to each patient daily. Response time was evaluated from the beginning of medication use until loss of response, toxicity or medical decision to cease treatment. Results Thirty-three patients were evaluated. The median age at the beginning of medication administration was 29 years. Patients had received a median of five prior therapies. Overall response rate was 45.4%, with 13 patients achieving partial response, two achieved clinical response, 14 remained with stable disease, two had disease progression, and two were not evaluated. Patients received a median of 14 cycles. Progression-free survival was nine months, and overall survival was estimated to be 36 months. Three patients used the medication for more than four years. The most frequently reported adverse events were thrombocytopenia and hypercholesterolemia. Three patients had pulmonary toxicity. Grade III and IV adverse events occurred in 39% of the patients. Conclusion Everolimus was found to provide a response in a group of patients with refractory or relapsed Hodgkins lymphoma who had adequate tolerability to the drug.

Disseminated fusariosis with endophthalmitis in a patient with hematologic malignancy

1 Hospital Albert Einstein, Sao Paulo, SP, Brasil. Autor correspondente: Guilherme Fleury Perini – Hospital Israelita Albert Einstein, Istituto Israelita de Ensino e Pesquisa, Avenida Albert Einstein, 627/701, Bloco A – Morumbi – CEP: 05652-900 – Sao Paulo, SP, Brasil – Tel.: (11) 2151-8709 – E-mail: guiperini@einstein.br Data de submissao: 2/8/2012 – Data de aceite: 24/2/2013 Figura 1. Tomografia computadorizada de orbitas mostrando delaminacao lateral, medial e anterior do globo ocular esquerdo, compativel com endoftalmite Figura 2. Exame anatomopatologico do olho esquerdo, mostrando abscesso intraocular