Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations

Abstract

The abnormal multimeric composition of plasma von Willebrand factor in type IIB von Willebrand's disease is transiently corrected after infusion of 1-deamino-[8-D-arginine]-vasopressin. However, the larger multimers released into the circulation disappear more rapidly in these patients than in type I von Willebrand's disease or normals. We demonstrate that the larger multimers of normal von Willebrand factor transfused into a type IIB patient are cleared from the circulation more slowly than multimers of similar size endogenously released from tissue stores. The rate of disappearance of large von Willebrand factor multimers after infusion of cryoprecipitate is similar in IIB, IIA, and severe homozygous-like von Willebrand's disease. Platelets from the IIB patient exhibited normal ristocetin-induced binding of normal von Willebrand factor. However, like normal platelets, they bound IIB von Willebrand factor at lower ristocetin concentrations than required for normal von Willebrand factor. These findings provide evidence that absence of the larger multimers from IIB plasma is related to a molecular abnormality of von Willebrand factor rather than to enhanced affinity of abnormal tissue or cellular binding sites, as is the case in the recently described “pseudo” von Willebrand's disease and “platelet-type” von Willebrand's disease.

Pre‐chemotherapy white blood cell depletion by therapeutic leukocytapheresis in leukemia patients: A single‐institution experience

“…Although the WBC count is usually greater in ALL and CML, these patients are less likely to have serious complications attributed to hyperleukocytosis, due to the lower cell volume of lymphoblasts in ALL and differentiated WBCs in CML, compared with myeloblasts in AML . According to Lichtman et al, lymphoblasts have a low mean cell volume (250‐350 μm 3 ), compared to myeloblasts (350‐450 μm 3 ) . Also, because WBCs are not as deformable as red blood cells, viscosity increases logarithmically as the fractional volume of WBCs increases .…”

“…According to Lichtman et al, lymphoblasts have a low mean cell volume (250‐350 μm 3 ), compared to myeloblasts (350‐450 μm 3 ) . Also, because WBCs are not as deformable as red blood cells, viscosity increases logarithmically as the fractional volume of WBCs increases . An additional risk is greater rates of oxygen consumption of blasts, which can lead to further ischemia in tissues .…”

“…Also, because WBCs are not as deformable as red blood cells, viscosity increases logarithmically as the fractional volume of WBCs increases . An additional risk is greater rates of oxygen consumption of blasts, which can lead to further ischemia in tissues . According to Porcu et al, there seems to be “a point of no return” in leukostasis, beyond which even rapid WBC reduction would be ineffective …”

“…Leukostasis is associated with deterioration of organ function due to thrombosis, hypoxia, tissue infiltration, and hemorrhage . Symptoms of leukostasis include respiratory distress, neurological signs (headache, blurred vision, confusion, lethargy, stupor, seizure, coma, papilledema) and thrombotic complications …”

Leucodepletion for hyperleucocytosis – first report on a novel technology featuring electronic interphase management

“…In the age of tyrosine kinase inhibitors, excessive neutrophilia, as previously frequently observed in patients with chronic‐phase chronic myeloid leukaemia, has become a rare event . Besides treatment of leucostasis, the goal of leucodepletion can be debulking of leukaemia cell load, to prevent sequelae of excessive tumour cell destruction, such as tumour lysis syndrome and disseminated intravascular coagulopathy, although this is not supported by strong formal clinical evidence . All leucodepletion systems have in common the establishment of an extracorporeal circulation, the separation of cellular and noncellular blood components in a centrifuge and the selective removal of leucocytes .…”