Therapeutic Leukocytapheresis Research Articles

Does severe anemia necessitate red cell transfusion before therapeutic leukocytapheresis in patients with hyperleukocytosis and suspected tumor lysis syndrome? Addressing a transfusion decision dilemma

Does severe anemia necessitate red cell transfusion before therapeutic leukocytapheresis in patients with hyperleukocytosis and suspected tumor lysis syndrome? Addressing a transfusion decision dilemma

Therapeutic Leukocytapheresis to relieve priapism due to leukostasis in CML patients: Our experience in a tertiary care centre

Hyperleukocytosis in leukemic patients may cause tumour lysis syndrome, disseminated intravascular coagulopathy, and leukostasis, resulting in decreased tissue perfusion and increasing the risk of mortality. Since the myeloid blasts are larger than lymphoid blasts and are less deformable, complications of leukostasis are seen more frequently in myeloid leukemia. Priapism is a less common complication associated with leukostasis in leukaemia patients that should be treated as soon as possible to avoid ischemic injuries. Although chemotherapeutic drugs such as hydroxyurea and imatinib are used to treat hyperleukocytosis in CML patients, leukocytapheresis (LCP) can achieve rapid cytoreduction. Prophylactic LCP could not offer any advantage over aggressive chemotherapy, but therapeutic leukocyte depletion has a proven role in patients having symptomatic leukostasis due to high tumour burden. Three patients with ischaemic priapism were reported at our institute's emergency department, where detumescence could not be achieved by distal shunting or aspiration with phenylephrine instillation. The procedure of therapeutic LCP was performed in all three patients on an emergency basis, which resolved painful priapism by rapid cytoreduction.

TRAFFIC JAM IN THE VASCULATURE: A CASE OF PULMONARY LEUKOSTASIS

TRAFFIC JAM IN THE VASCULATURE: A CASE OF PULMONARY LEUKOSTASIS

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

Hyperleukocytosis is commonly seen in acute and chronic leukemias. Therapeutic leukocytapheresis using an automatic cell separator can help to achieve prompt leukoreduction to reduce the rate of thrombotic events and early mortality as well as to prevent tumor lysis syndrome. In this study, we report a single center's experience in managing leukemia patients with therapeutic leukocytapheresis prior to chemotherapy. Leukocytapheresis procedures were performed in 192 leukemia patients (including acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL], and chronic myeloid leukemia [CML]) with hyperleukocytosis between January and December 2016. Median % reduction of white blood cell (WBC) count was 30.5% and median % removal efficiency was 46.7% for 75 procedures where the waste bag was sampled. WBC removal efficiency strongly depended on diagnosis (and was 71%, 66%, and 39% for ALL, AML, and CML, respectively). Procedures were generally well tolerated with only 9 out of 192 patients having mild adverse effects. In the absence of specific guidelines for the management of hyperleukocytosis, leukocytapheresis in association with chemotherapy should be considered early in clinical practice.

Therapeutic leukocytapheresis in infants and children with leukemia and hyperleukocytosis: A single institution experience.

Hyperleukocytosis, defined as white blood cell (WBC) count above 100×109 /L, has high early morbidity and mortality from leukostasis-related complications, namely intracranial hemorrhage and pulmonary distress. Initiating chemotherapy without prior leukocytoreduction may lead to tumor lysis syndrome (TLS). Therapeutic leukocytapheresis (TL) is used as one leukocytoreductive intervention; however, its safety and efficacy in pediatric leukemia has not been established. The purpose of this study is to evaluate safety of TL in pediatric patients and assess the efficacy of TL in reducing WBC count in pediatric leukemia. Retrospective chart review was conducted on 14 patients with acute lymphoblastic leukemia (ALL) and 5 with acute myeloid leukemia (AML) who underwent TL during the period 2000-2014 at a single institution. Mean WBC count of 19 patients who received TL was 483.2×109 /L (547.1 in ALL, 304.3 in AML); a portion of patients presented with central nervous system symptoms (15%), respiratory symptoms (10%), or both (10%). TL reduced WBC count (mean 50.7% reduction after a single TL procedure; additional 17.1% reduction after a second TL procedure in 6 patients). Short-term survival immediately following TL was 100% without any major procedural complication. Mean survival time in patients with AML was 1.5years and with ALL was 6.5years. TL significantly reduces WBC number in pediatric leukemia patients as young as 22days old. In our retrospective study, TL was not associated with any significant complications and suggests that TL is a safe initial procedure in pediatric leukemia.

Use of hydroxyethyl starch in leukocytapheresis procedures does not increase renal toxicity

Hydroxyethyl starch (HES) is reportedly associated with an increased risk of renal failure and death when used for fluid resuscitation in critically ill patients. HES can be used during therapeutic leukocytapheresis (TL) procedures to enhance cell separation. The purpose of this study was to evaluate the occurrence of adverse events associated with HES during TL procedures. We performed a retrospective review of patients who underwent TL with and without HES in the period 2009 to 2013 at six academic medical institutions. A difference-in-difference regression analysis was used to estimate the mean change before and after TL in selected outcomes in the HES group relative to the average change in the non-HES group. Selected outcomes included serum creatinine, estimated glomerular filtration rate (eGFR), and white blood cell (WBC) count. A total of 195 patients who underwent 278 TL procedures were studied. We found no significant differences in serum creatinine levels and eGFR on Days 1 and 7 after TL procedure between patients who received and those who did not receive HES. The rate of adverse events and overall and early mortality were similar in both groups. Patients with acute myeloid leukemia who received HES had greater WBC reduction when HES was used. Additionally, patients who received HES had improvement in pulmonary leukostasis symptoms. HES, used at low doses during TL procedures, was not associated with adverse events previously ascribed to its use as a volume expander.

Therapeutic leukapheresis: 9-year experience in a University Hospital.

Hyperleucocytosis is associated with higher morbidity and mortality related to possible development of leucostasis, tumour lysis syndrome and/or disseminated intravascular coagulation. There is insufficient evidence of the need for leukocytapheresis during early treatment of hyperleucocytosis, and its efficiency remains controversial, although leucoreduction is a measure that can prevent adverse events and death. The aim of this study was to analyse the safety and effectiveness of therapeutic leukocytapheresis and its influence on early mortality in our case series, adjusted to independent mortality risk factors described in the literature. This was a retrospective review (June 2003-June 2012) of procedures carried out for the treatment of hyperleucocytosis at the Haematology and Haemotherapy Service of Miguel Servet University Hospital. The patients' data and technical information were prospectively registered for each leukocytapheresis session. Thirteen patients underwent a total of 27 leukocytapheresis procedures. After an average of two sessions, a statistically significant drop in the initial leucocyte counts was observed (p<0.01), as well as a relevant drop in lactate dehydrogenase levels. The only analytical value statistically related to early mortality in univariate analysis was initial creatinine level greater than 1.2 mg/dL (p=0.012, OR=2.5). Despite the small size and limited homogeneity of our case series, we can conclude that leukocytapheresis is a safe and effective therapeutic measure for leucoreduction in haematological pathologies of any lineage, particularly in patients without acute myeloid leukaemia. Patients with acute myeloid leukaemia had worse outcomes within 6 months of having finished leukocytapheresis sessions, as well as in terms of mean global survival and mean time of mortality. However, global mortality rates were similar in patients with or without acute myeloid leukaemia.

Questionnaire Based Assessment of Patients' Acceptability of Leukocytapheresis for the Treatment of Inflammatory Bowel Disease

The aim of the present study was to assess patients' acceptance of therapeutic leukocytapheresis known as cytapheresis (CAP) for the treatment of an active flare of inflammatory bowel disease (IBD). A questionnaire was sent to 155 IBD patients who had been treated with CAP for an active flare of IBD at the IBD center of Hyogo College of Medicine between January 2009 and July 2012. In the questionnaire, patients were asked to evaluate CAP including efficacy, safety, unfavorable features and their willingness to be retreated with CAP for a subsequent IBD flare-up. Seventy-eight percent (112 of 155 patients) including 86 with ulcerative colitis and 26 with Crohn's disease completed the questionnaire. The need for coming to hospital for CAP, needle pain during blood access, sparing time for CAP process were scored by 57%, 58%, and 58.9% of the patients, respectively as unfavorable. Patients highly favored the safety of CAP, the sum of very and relatively favorable was 89%, higher than for efficacy (68%). Seventy-two percent of patients favored retreatment with CAP. In binary logistic regression analysis, the levels of satisfaction for efficacy (P < 0.001), and inconvenience for CAP treatment time (P < 0.001) were highly significant factors for patients' willingness to be retreated. Bearing in mind that CAP is a non-pharmacologic treatment intervention, our analyses indicated that IBD patients favored high efficacy, as well as comfort of CAP or maintaining their normal social activity even during an active phase of the disease. Patient's acceptability for CAP appeared to be determined by the balance of these factors.

Leukocyte Depletion by Therapeutic Leukocytapheresis in Patients with Leukemia

Hyperleukocytosis is a complication of various leukemias and can result in life-threatening leukostasis. Critical white blood cell (WBC) counts are conventionally defined as higher than 100 × 10⁹/l in acute myeloid leukemia and > 300 × 10⁹/l in acute lymphatic leukemia and other leukemic disorders (e. g. chronic myeloid leukemia). Leukocytapheresis is a therapeutic tool to reduce leukocyte counts in patients with symptomatic or threatening leukostasis until induction chemotherapy works. In patients with temporary contraindications against cytotoxic drugs, e.g. during pregnancy, leukocytapheresis can be used as a bridging therapy until conventional chemotherapy can be started. Therapeutic leukocytapheresis should be performed in specialized centers by experienced, well-trained staff. Thorough monitoring of the patients is extremely relevant. During a single procedure, WBC count can be reduced by 10–70%. Treatment should be repeated daily and can be discontinued when the symptoms of leukostasis have been resolved and/or leukocyte counts have fallen below the critical thresholds. There are no prospective studies evaluating the clinical efficacy of therapeutic leukocytapheresis in patients with hyperleukocytosis. It can be concluded from retrospective studies that leukocytapheresis might have some beneficial effect in early morbidity and mortality of patients with newly diagnosed AML but has no influence on overall long-term survival. Induction chemotherapy is the most important treatment in these patients and must never be postponed.

Therapeutic leukocytapheresis in inflammatory bowel disease: clinical efficacy and mechanisms of action

Intense infiltration of the intestinal mucosa by activated leukocytes is a hallmark of inflammatory bowel disease (IBD). Therefore, removal of circulating leukocytes may be an attractive approach for treating IBD. Leukocytapheresis with Cellsorba, a column of polyethylenephtarate fibers that captures monocytes, granulocytes and lymphocytes, has been used to treat IBD, particularly ulcerative colitis, in Japan and Europe. This article reviews the clinical efficacy and safety data and the mechanisms of action of leukocytapheresis in IBD. Although the majority of clinical studies enrolled only small numbers of patients and had open-labeled designs, leukocytapheresis showed clinical efficacy with an excellent safety profile. Leukocytapheresis depletes granulocytes, monocytes, lymphocytes and platelets, alters cell population profiles, modulates cytokine production, and induces bone marrow-derived cells. In conclusion, leukocytapheresis exerts anti-inflammatory and tissue-repairing effects on the intestinal mucosa in IBD. Further studies are needed to explain the exact mechanism of action and to determine the true efficacy of this approach.

Developments in the apheresis procedure for the treatment of inflammatory bowel disease

Initially used to treat rheumatoid arthritis, nonselective therapeutic leukocytapheresis was applied to the treatment of inflammatory bowel disease (IBD) as early as the 1980s. Since then, the process has been further refined and 2 blood perfusion systems using membrane filtration are presently employed in Japan and Europe for the selective removal of leukocytes in patients with IBD: Cellsorba is a column of polyethylenephtarate fibers that captures lymphocytes and granulocytes, and Adacolumn is a column of cellulose acetate beads that selectively adsorb granulocytes and monocytes. These systems overcome the limitations of centrifugation. Leukocytapheresis has been shown to exert an overall anti-inflammatory effect, as peripheral leukocytes demonstrated a diminished capacity to produce inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, IL-6, IL-8, and IL-1beta. In addition, down-regulation in the expression of adhesion molecule L-selectin and a shift toward a more immature granulocyte phenotype were observed in the peripheral blood. The safety and beneficial therapeutic effect of leukocytapheresis in IBD are being investigated further.