Therapeutic leukocytapheresis for improvement in respiratory function in a woman with hyperleukocytosis and mantle cell lymphoma with a circulating small lymphocyte phenotype

Mantle cell lymphoma is an aggressive malignant B‐cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature‐appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10³/µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two‐whole‐blood‐volume leukocytapheresis reduced her WBC from 465 to 221 × 10³/µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO₂) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398–402, 2016. © 2015 Wiley Periodicals, Inc.     

Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis

BACKGROUND: The optimal management of childhood acute lymphoblastic leukemia (ALL) with hyperleukocytosis is unclear, largely because the risk of leukostasis-related complications is poorly characterized. PROCEDURE: We reviewed the presenting characteristics, initial management, and frequency and type of complications in all children seen at St. Jude Children's Research Hospital with previously untreated ALL and an initial leukocyte count >200 x 10(9)/L. RESULTS: A total of 178 children, representing 8% of all children with ALL, had an initial leukocyte count >200 x 10(9)/L; 67 patients had a leukocyte count >400 x 10(9)/L. Sixteen patients (9%) had neurological complications with 12 of these patients experiencing symptoms at presentation. Four patients (2%), all with initial leukocyte counts >400 x 10(9)/L, suffered a CNS hemorrhage. Pulmonary leukostasis occurred in 11 patients (6%). The degree of hyperleukocytosis was significantly predictive of neurological (P = 0.006) and respiratory (P = 0.014) complications. The majority of complications occurred at presentation. Cytoreduction (94 patients) decreased the leukocyte count but delayed initiation of chemotherapy (P = 0.013). CONCLUSIONS: Serious leukostasis-related complications are relatively uncommon in childhood ALL and most occur at presentation. Their incidence increases in proportion to the leukocyte count. A large subset of cases can be managed successfully without cytoreduction. Cytoreduction may be considered for patients with leukocyte counts >400 x 10(9)/L or patients who have complications at presentation.     

Experimental studies on the adult respiratory distress syndrome: effects of induced DIC; granulocytes and elastase in mini pigs

The potential role of granulocyte proteinases on experimentally induced ARDS was evaluated. In order to investigate the acute effects on lung function, elastase (330 U kg-1h-1) or thrombin (75-150 U kg-1 h-1) was continuously infused into anaesthetized and mechanically ventilated mini pigs. Both elastase as well as thrombin induced a progressive respiratory failure with prompt increase in pulmonary vascular resistance, and decrease of cardiac output, further a pulmonary leukostasis, and a disturbance of blood coagulation leading to hypocoagulability. High proteolytic activity selectively in the lung indicates a possible role of proteinases released from sequestered polymorphonuclear neutrophils. Similar results following elastase infusion were however obtained in leukopenic animals pretreated with a single dose of dimethylmyleran (5 mg kg-1) which depleted the granulocytes totally. These results offer the possibility that elastase itself may cause respiratory failure and lung tissue damage. On the other hand the digestion pattern of phosphorylase kinase by lung tissue homogenates of thrombin- or elastase-infused mini pigs clearly indicates that elastase is only one of several mediators which may cause experimentally induced ARDS even in the absence of granulocytes.     

Grading of symptoms in hyperleukocytic leukaemia: a clinical model for the role of different blast types and promyelocytes in the development of leukostasis syndrome

OBJECTIVE: Patients with hyperleukocytic leukaemia were graded according to the severity of symptoms possibly caused by leukostasis to evaluate the effectiveness of therapy and to test the relative contribution of blast type and count of blasts and promyelocytes in the development of leukostasis syndrome. METHODS: Ninety-five patients (59 male, 36 female, median age 52 yr) with hyperleukocytic leukaemia [leukocytes above 50 x 10(9)/L, 48 acute myeloid leukaemia (AML), 31 chronic myeloid leukaemia (CML), 13 acute lymphoblastic leukaemia (ALL), three chronic myelomonocytic leukaemia (CMML)] were grouped according to the presence or absence and severity of neurologic, pulmonary and other symptoms into four categories (no, possible, probable and highly probable leukostasis syndrome). Age, white blood count (WBC), haemoglobin, blast count and total of blasts plus promyelocytes of these groups were compared by Mann-Whitney U-test. RESULTS: Patients with myeloid leukaemia (AML M1/M2, CML) which scored as highly probable leukostasis showed significantly higher WBC (P = 0.011), lower haemoglobin (P = 0.004), higher peripheral blast counts (P = 0.004) and higher total of peripheral blasts plus promyelocytes (P < 0.001) compared with the lower probability groups. In leukaemia involving the monocytic lineage (AML M4/M5, CMML) no significant differences were found in any of these factors between patients with highly probable leukostasis and the other patients. CONCLUSIONS: Our results show that a four-stage clinical grading scale is a valuable tool for analysing hyperleukocytic patient populations and evaluate the effectiveness of therapy more precisely. We further demonstrate that the mechanisms of leukostasis are different in myeloid leukaemia as compared with leukaemia with involvement of the monocytic lineage.     

高白细胞白血病研究现状

白血病患者周围血象中白细胞计数超过100×109/L时称为高白细胞白血病(HLL),发生率约占白血病的10%~20%。HLL属高危型白血病,病理生理基础是白细胞淤滞,临床可发生出血、急性呼吸窘迫综合征(ARDS)、弥散性血管内凝血(DIC)等严重危及生命的并发症,早期病死率高达30%~54%。治疗上需迅速降低白细胞数目,减少并发症的发生,以进一步行正规化疗。     

Therapeutic leukapheresis in patients with leukostasis secondary to acute myelogenous leukemia

Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French‐American‐British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 × 10⁹/L to 150.3 × 10⁹/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.     

Role of angiotensin II in retinal leukostasis in the diabetic rat

To study if the endogenous renin-angiotensin system affects diabetic retinal leukostasis, rats with streptozotocin-induced diabetes were treated with an ACE inhibitor (ramipril), an angiotensin II AT(1) receptor antagonist (losartan) and the Ca channel blocker, (nifedipine). In the diabetic rats, these drug treatments reduced systolic blood pressure by approximately 16 mmHg but did not change blood glucose. After 2 weeks, the rats were examined for retinal leukostasis in vivo with a scanning laser ophthalmoscope (SLO). Retinal leukostasis, which was defined as no movement of arrested leukocytes over 2 min, was markedly higher in diabetic rats than normal controls (P<0.01). Leukostasis was significantly decreased by ramipril and losartan (P<0.01 vs. untreated diabetic rats) but was still higher than normal. Retinal leukostasis after nifedipine treatment was not significantly different than in untreated diabetic rats. The same trend was observed when leukostasis was analyzed on retinal flat mounts with concanavalin A and CD45 immunofluorescence; ramipril and losartan treatment, however, decreased leukostasis to values no different than controls. Retinal leukostasis was lowered by nifedipine (P<0.05, untreated diabetes vs. nifedipine-treated) but was still higher than in normal, ramipril-, or losartan-treated rats. Assays of gene expression of retinal intercellular adhesion molecule (ICAM-1) by semi-quantitative RT-PCR indicated that ICAM-1 mRNA was increased in diabetic rats but was decreased markedly by treatment with losartan or ramipril, and modestly by nifedipine. In summary, suppressing the activity of the endogenous renin-angiotensin system markedly decreases, perhaps even normalizes, the retinal leukostasis that accompanies type I diabetes in rats. These effects seem to be partly independent of blood pressure and to be associated with a decrease in ICAM-1 gene expression. Angiotensin II may, thus, mediate retinal leukostasis in early diabetes.