Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with HIV infection. However, PBL can also be seen in patients with other immunodeficiencies as well as in immunocompetent ...individuals. Because of its distinct clinical and pathological features, such as lack of expression of CD20, plasmablastic morphology, and clinical course characterized by early relapses and subsequent chemotherapy resistance, PBL can represent a diagnostic and therapeutic challenge for pathologists and clinicians alike. Despite the recent advances in the therapy of HIV-associated and aggressive lymphomas, patients with PBL for the most part have poor outcomes. The objectives of this review are to summarize the current knowledge on the epidemiology, biology, clinical and pathological characteristics, differential diagnosis, therapy, prognostic factors, outcomes, and potential novel therapeutic approaches in patients with PBL and also to increase the awareness toward PBL in the medical community.
How we manage Bing–Neel syndrome Castillo, Jorge J.; Treon, Steven P.
British journal of haematology,
November 2019, Letnik:
187, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
Bing–Neel syndrome (BNS) is an uncommon presentation of Waldenström macroglobulinaemia (WM), seen during the course of the disease in about 1% of patients. BNS occurs when WM cells gain ...access to the central nervous system (CNS) causing neurological deficits. The diagnosis of BNS is suggested by the presence of radiological abnormalities, such as leptomeningeal enhancement on magnetic resonance imaging and confirmed by the presence of clonal lymphoplasmacytic cells and MYD88 L265P in the cerebrospinal fluid. The treatment of BNS requires agents with good penetration into the CNS, such as fludarabine, methotrexate and cytarabine. The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS‐penetrating properties, and recent data suggest a therapeutic role in BNS. In this review, we will discuss the clinical and pathological features, diagnostic criteria, treatment options and outcomes of patients with BNS.
Hyponatremia, a common electrolyte abnormality in oncology practice, may be a negative prognostic factor in cancer patients based on a systematic analysis of published studies. The largest body of ...evidence comes from small‐cell lung cancer (SCLC), for which hyponatremia was identified as an independent risk factor for poor outcome in six of 13 studies. Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with SCLC than with other malignancies. SIADH may be driven by ectopic production of arginine vasopressin (AVP) by tumors or by effects of anticancer and palliative medications on AVP production or action. Other factors may cause hypovolemic hyponatremia, including diarrhea and vomiting caused by cancer therapy. Hyponatremia may be detected on routine laboratory testing before or during cancer treatment or may be suggested by the presence of mostly neurological symptoms. Treatment depends on several factors, including symptom severity, onset timing, and extracellular volume status. Appropriate diagnosis is important because treatment differs by etiology, and choosing the wrong approach can worsen the electrolyte abnormality. When hyponatremia is caused by SIADH, hypertonic saline is indicated for acute, symptomatic cases, whereas fluid restriction is recommended to achieve a slower rate of correction for chronic asymptomatic hyponatremia. Pharmacological therapy may be necessary when fluid restriction is insufficient. The orally active, selective AVP receptor 2 (V2)‐receptor antagonist tolvaptan provides a mechanism‐based option for correcting hyponatremia caused by SIADH or other conditions with inappropriate AVP elevations. By blocking AVP effects in the renal collecting duct, tolvaptan promotes aquaresis, leading to a controlled increase in serum sodium levels.
The rationale for the diagnosis and management of hyponatremia in cancer patients is identified, the main causes are reviewed, and treatment options are discussed with a focus on the practical use of the arginine vasopressin antagonist tolvaptan.
With the worldwide approval of the oral covalent Bruton tyrosine kinase (BTK) inhibitors ibrutinib and zanubrutinib for treating patients with Waldenström macroglobulinemia (WM), targeted agents have ...certainly taken center stage in the therapeutic landscape of WM. This review discusses the biological and clinical data supporting current and up-and-coming targeted agents in WM. Bruton tyrosine kinase inhibitors induce fast, deep, and durable responses in patients with WM, comparable to chemoimmunotherapy; however, there is a glaring absence of comparative studies between these regimens. The high response and progression-free survival rate and the ease of administration of BTK inhibitors must be balanced against their specific adverse-event profile with unique toxicity (e.g., bleeding and cardiac arrhythmia) and the indefinite duration of the therapy. Novel targeted agents of interest include BCL2 antagonists (e.g., venetoclax and sonrotoclax) and non-covalent BTK inhibitors (e.g., pirtobrutinib and nemtabrutinib), among others. The therapeutic landscape of patients with WM will benefit from the robust participation of patients in clinical trials.
MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. ...CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib.
We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenström's macroglobulinemia who had received at least one previous treatment, and we investigated the effect of MYD88 and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was administered orally until disease progression or the development of unacceptable toxic effects.
After the patients received ibrutinib, median serum IgM levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter, and bone marrow involvement decreased from 60% to 25% (P<0.01 for all comparisons). The median time to at least a minor response was 4 weeks. The overall response rate was 90.5%, and the major response rate was 73.0%; these rates were highest among patients with MYD88(L265P)CXCR4(WT) (with WT indicating wild-type) (100% overall response rate and 91.2% major response rate), followed by patients with MYD88(L265P)CXCR4(WHIM) (85.7% and 61.9%, respectively) and patients with MYD88(WT)CXCR4(WT) (71.4% and 28.6%). The estimated 2-year progression-free and overall survival rates among all patients were 69.1% and 95.2%, respectively. Treatment-related toxic effects of grade 2 or higher included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%), which were more common in heavily pretreated patients; postprocedural bleeding (in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and atrial fibrillation associated with a history of arrhythmia (5%).
Ibrutinib was highly active, associated with durable responses, and safe in pretreated patients with Waldenström's macroglobulinemia. MYD88 and CXCR4 mutation status affected responses to this drug. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01614821.).
HOLA! from Latin America to the myeloma world Castillo, Jorge J.
British journal of haematology,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
188, Številka:
3
Journal Article
BACKGROUND.: Prognostic factors and outcomes in patients with marginal zone lymphoma (MZL) have been studied in small cohort studies, which may not reflect the population at large. METHODS.: Clinical ...characteristics and survival outcomes of adult patients with MZL who were diagnosed between 1995 and 2009 were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. The authors generated clinical prognostic models for subtypes of MZL and compared survival during the periods of 1995 through 2000, 2001 through 2004, and 2005 through 2009. RESULTS.: The prognosis was significantly better for patients with mucosa-associated lymphoid tissue (MALT) lymphoma (5-year relative survival rate of 88.7%; P < .0001) compared with those with the splenic MZL (SMLZ)or nodal MZL (NMZL) subtypes (5-year relative survival rates of 79.7% and 76.5%, respectively). There was evidence of improved outcomes in patients with NMZL and MALT lymphomas between 1995 and 2009 (P < .0001), with no difference noted in patients with SMZL (P = .56). Advancing age and the presence of B symptoms had prognostic significance in all MZL subtypes. Male sex and stage of disease were significant only for the NMZL and MALT categories. Survival in patients with MALT lymphomas varied depending on the site of origin, with a worse prognosis noted in those with gastrointestinal and pulmonary locations of origin (5-year incidence rate of lymphoma-related death, 9.5%-14.3%) compared with ocular, cutaneous, and endocrine sites (4.5%-7.8%; P < .0001). CONCLUSIONS.: The survival for patients with SMZL is similar to that for those with NMZL, and unlike the NMZL and MALT subtypes, it has not improved over the past decade. The prognosis of patients with MALT lymphoma varies according to the anatomical site of origin.
PDF
