Hyperleukocytosis increases risk of fatal hyperkalemia with new ibrutinib/venetoclax regimen for refractory mantle cell lymphoma.

Background: A recent phase 2 study reported success using combination of ibrutinib and venetoclax for relapsed/refractory mantle cell lymphoma (MCL). We report a case of MCL with hyperleukocytosis that developed fatal hyperkalemia after a single low initiation dose of venetoclax.Case report: A 72-year-old man with known MCL was admitted for hyperkalemia and anemia (Hgb = 6.6 g/dL, K+ =9.6 mmol/L). Repeated K+ measurements and clinical evaluation were consistent with pseudohyperkalemia. The patient's lymphocyte count had risen from 15.2 to 466.8 K/uL in the preceding 1.5 months despite 8 cycles of ibrutinib. Based on the results of a recent phase 2 study Venetoclax was added; after a single very low initiation dose of venetoclax the patient developed fatal hyperkalemia.Discussion: The proliferation of new therapies is making difficult to perform randomized clinical trials large enough to capture potential risks of new therapies in specific scenarios. Fatal hyperkalemia resulted from use of a recently recommended combination regimen for refractory/relapsed MCL in a phase 2 study, despite dose escalation and TLS prophylaxis suggesting increased risk of this regimen for patients with hyperleukocytosis.

Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms in Patients with Advanced Cancer.

The use of an automated text messaging intervention provided a cost-effective option for symptom management for patients experiencing cancer-related symptoms.

Human herpesvirus 6 is associated with status epilepticus and hyponatremia after umbilical cord blood transplantation.

Status epilepticus after allogeneic hematopoietic cell transplantation (alloHCT) is rare. The authors report a case involving a 65-year-old man with nonconvulsive status epilepticus 34 days after umbilical cord blood transplantion for chronic lymphocytic leukemia. Cerebrospinal fluid and serum were positive for human herpesvirus 6 (HHV6). Magnetic resonance imaging of the brain showed symmetric T2 hyper-intensity bilaterally in the mesial temporal lobes, and T2 hyperintensi-ties and restricted diffusion of bilateral putamina. Despite aggressive anticonvulsive therapy, his seizures only abated with initiation of ganciclovir therapy. The patient completed six weeks of combination antiviral therapy (ganciclovir and foscarnet). His cognitive function gradually improved and, after prolonged rehabilitation, the patient was discharged home with residual intermittent memory loss but otherwise functional. HHV6 should be considered in the differential diagnosis of nonconvulsive status epilepticus after alloHCT, especially in patients with hyponatremia. Empirical antiviral therapy targeting HHV6 should be administered to these patients.

L'état de mal épileptique est rare après une greffe de cellules souches hématopoïétiques allogéniques (GCSallo). Les auteurs rendent compte du cas d'un homme de 65 ans présentant un état de mal épileptique non convulsif 34 jours après avoir subi une greffe de sang de cordon pour soigner une leucémie lymphocytaire chronique. Le liquide céphalorachidien et le sérum étaient positifs à l'herpèsvirus humain type 6 (HVH6). L'imagerie par résonance magnétique du cerveau a révélé un signal hyperintense symétrique et bilatéral des lobes temporaux mésiaux en T2, ainsi que des signaux hyperintenses en T2 et une diffusion bilatérale restreinte du putamen. Malgré un traitement énergique aux anticonvulsivants, les convulsions n'ont diminué qu'après l'amorce d'un traitement au ganciclovir. Le patient a été mis sous bithérapie antivirale (ganciclovir et foscarnet) pendant six semaines. Sa fonction cognitive s'est améliorée graduellement et, après une réadaptation prolongée, il a obtenu son congé à domicile. Il présentait une perte de mémoire résiduelle intermittente, mais était autrement fonctionnel. Il faut envisager un HVH6 dans le diagnostic différentiel de l'état de mal épileptique non convulsif après une GCSallo, particulièrement chez les patients présentant une hyponatrémie. Il faut administrer une anti-virothérapie empirique qui cible l'HVH6 chez ces patients.

Functional expression of TRESK-2, a new member of the tandem-pore K+ channel family.

A new member of the tandem-pore K+ (K(2P)) channel family has been isolated from mouse testis complementary DNA. The new K(2P) channel was named TRESK-2, as its amino acid sequence shares 65% identity with that of TRESK-1. Mouse TRESK-2 is a 394-amino acid protein and possesses four putative transmembrane segments and two pore-forming domains. TRESK-2 has a long cytoplasmic domain joining the second and third transmembrane segments and a short carboxyl terminus. In the rat, TRESK-2 mRNA transcripts were expressed abundantly in the thymus and spleen and at low levels in many other tissues, including heart, small intestine, skeletal muscle, uterus, testis, and placenta, as judged by Northern blot analysis. TRESK-2 mRNA was also expressed in mouse and human tissues. In COS-7 cells transfected with TRESK-2 DNA, a time-independent and noninactivating K+-selective current was recorded. TRESK-2 was insensitive to 1 mm tetraethylammonium, 100 nm apamin, 1 mm 4-aminopyridine, and 10 microm glybenclamide. TRESK-2 was inhibited by 10 microm quinidine, 20 microm arachidonate and acid (pH 6.3) at 49, 43, and 23%, respectively. Single channel openings of TRESK-2 showed marked open channel noise. In symmetrical 150 mm KCl, the current-voltage relationship of TRESK-2 was slightly inwardly rectifying, with the single channel conductance 13 picosiemens (pS) at +60 mV and 16 pS at -60 mV. In inside-out patches, TRESK-2 was unaffected by the intracellular application of 10 microm guanosine 5'-O-(thiotriphosphate). These results show that TRESK-2 is a functional member of the K(2P) channel family and contributes to the background K+ conductance in many types of cells.