|Year : 2021 | Volume
| Issue : 2 | Page : 240-243
Efficacy of therapeutic leukapheresis in acute lymphoblastic leukemia presenting with leukostasis: A report of two cases
Tapti Mohapatra1, Prabodha Kumar Das2
1 Department of Transfusion Medicine, Fortis Hospital, Bengaluru, Karnataka, India
2 Department of Medical Oncology/Haematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
|Date of Submission||12-Sep-2021|
|Date of Decision||18-Oct-2021|
|Date of Acceptance||19-Oct-2021|
|Date of Web Publication||30-Nov-2021|
Dr. Prabodha Kumar Das
Department of Medical Oncology/Haematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Therapeutic leukapheresis is performed in patients having hyperleukocytosis, leading to leukostasis. The aim of this study was to evaluate the efficacy of therapeutic leukapheresis in reducing white cell count in leukemic patients with symptoms of leukostasis. Two cases of acute lymphoblastic leukemia, admitted to the hematology intensive care unit between January and May 2015, were taken up for therapeutic leukapheresis, using COBE Spectra Cell Separator. The first patient was a 24-year-old male, admitted with fever, weakness, headache, blurred vision, and a total leukocyte count (TLC) of 564,000/μL. The second patient was a 36-year-old male admitted with fever, headache, dyspnea, and a TLC of 530,000/μL. The first patient had a 31.38% and 30.19% reduction in TLC after first and second procedures, respectively. The second patient had a reduction in TLC of 31.7% and 31.41% after first and second procedures, respectively. This significant decrease in white cell count achieved reversal of symptoms of leukostasis. Patients with hyperleukocytosis may present as a medical emergency, requiring prompt recognition and initiation of therapy to prevent respiratory failure or intracranial hemorrhage. Leukapheresis removes circulating blasts quickly to alleviate symptoms.
Keywords: Hyperleukocytosis, leukapheresis, leukostasis
|How to cite this article:|
Mohapatra T, Das PK. Efficacy of therapeutic leukapheresis in acute lymphoblastic leukemia presenting with leukostasis: A report of two cases. Glob J Transfus Med 2021;6:240-3
|How to cite this URL:|
Mohapatra T, Das PK. Efficacy of therapeutic leukapheresis in acute lymphoblastic leukemia presenting with leukostasis: A report of two cases. Glob J Transfus Med [serial online] 2021 [cited 2022 Aug 10];6:240-3. Available from: https://www.gjtmonline.com/text.asp?2021/6/2/240/331627
| Background|| |
Cell separators are routinely used for plateletpheresis, peripheral blood stem cell collections, and therapeutic plasma exchange. Therapeutic leukapheresis, particularly as an emergency procedure, has been uncommonly performed and reported. Therapeutic leukapheresis is performed in patients with hyperleukocytosis, a condition where white blood cell (WBC) counts are more than 100,000/uL.
Hyperleukocytosis leads to leukostasis, especially in brain and lungs, which leads to cerebrovascular insufficiency or pulmonary leukostasis, respectively; former characterized by weakness, headaches, and blurred vision, while the latter characterized by dyspnea, tachypnea, and hypoxemia without hypercapnia.
The increasing morbidity and mortality are attributes to hyperleukocytosis and its resultant microcirculatory dysfunction, a phenomenon known as leukostasis,, where the sludging of leukemic blasts in the capillary vessels and their adhesive interactions gives rise to deleterious effects.
The number of leukocytes necessary for leukostasis changes with each pathology, owing to among other factors, different morphological, molecular, and plasticity characteristics of the blast cells, as well as the capacity of the endothelial cells to release cytokines.
Besides the high blood viscosity as a physical mechanism for the microcirculatory disturbances, blast cells have been shown to secrete cytokines (IL-1β and TNF-β), leading to an upregulation of endothelial adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and thus a concomitant adhesion of blasts on the endothelium.
In acute myeloid leukemia, leukostasis appears at leukocyte counts above 100 × 109/L in acute lymphoblastic leukemia (ALL); and severe symptoms appear above 400 × 109/L in ALL; however, symptoms do not appear in chronic lymphocytic leukemia until the leukocyte count exceeds 500 × 109/L.
It is recognized that hyperleukocytosis is an unfavorable prognostic factor where higher risk of relapse and shorter survival rates are commonly seen.
The rapid destruction of leukemic cells in response to chemotherapy also causes metabolic disturbances (tumor lysis syndrome). This has led to the notion that prompt cytoreduction is imperative in preventing the high incidence of hyperleukocytic leukemia-related complications and early deaths.
Aims and objectives
The aim of the study was to evaluate the role of therapeutic leukapheresis in ALL.
| Case Report|| |
Most institutions have no ready protocol on when leukapheresis should be adhered to for new cases of hyperleukocytic leukemia. Decisions on leukapheresis are very much based on the discretion of the attending physician, severity of symptoms, and leukocyte counts. Patients have to be hemodynamically stable before leukapheresis procedure.
We retrospectively analyzed records of two patients, admitted to the hematology intensive care units of two institutes between January 2015 and May 2015, with ALL with leukocyte counts above 5 lakhs per microliter. In both the patients, leukapheresis was done using continuous-flow automated instrument (cell separator) (COBE Spectra), once correct placement of triple-lumen jugular vein catheter was confirmed by chest radiography. Preliminary workup included routine CBC, blood cultures, urine studies, bone marrow aspiration, and biopsy. Testing for infectious disease markers was also done.
A 24-year-old male weighing 55 kg was admitted with chief complaint of intermittent fever, weakness, tooth pain, headache, blurred vision, and decreased hearing for 2 months.
- Vitals on admission: On examination, he was pale, tachypneic with a respiratory rate of 60/minute, pulse 114/minute, temperature 102.6°C. He had purpuric spots over upper limb; bilateral pitting edema of upper and lower extremities. Generalized lymphadenopathy was absent. Abdominal examination showed mild distension, with palpable liver and spleen, but no free fluid. Decreased breath sounds in both lung fields were observed. Cardiovascular system was normal
- Admission laboratories: CBC – total leukocyte count (TLC): 540,000/μL, RBC: 2.8 × 106/μL, hemoglobin 8.4 g/dl, platelet: 55,000/μL, ESR 148 mm/h, and LDH 1708
- Peripheral smear: Atypical cells/blasts: 78%, metamyelocyte 5%, myelocyte 6%, N + B 70%, occasional nucleated RBC.
Bone marrow studies were positive for a diagnosis of ALL.
Ultrasound was positive for hepatosplenomegaly, bilateral pleural effusion. Chest X-ray was positive for opacity in the left lower lobe. Fundoscopy of eye was positive for Roth spots and flame-shaped hemorrhages.
Immunophenotyping studies were confirmative for ALL.
The patient was transferred to the intensive care unit and was stabilized with oxygen, antibiotics, diuretics, Foley catheter, and monitoring of strict input and output. One unit of packed red cells, fresh frozen plasma, and platelets was instituted.
Two leukapheresis procedures were done 48 h apart.
In the first procedure, inlet volume processed was 12,580 ml, and total blood volume was 3841 ml. Postprocedure, leukocyte count was 387,000/μL, the run time was 242 min, anticoagulant used was 949 ml.
A second procedure was done after 48 h. Inlet volume processed was 11,277 ml. Run time was 243 min, 1048 ml of anticoagulant wasused. Pre- and post-leukapheresis counts were 318,000/μL and 222,000/μL, respectively [Table 1].
A 36-year-old male weighing 47 kg was admitted with chief compliant of fever, headache, dyspnea, and generalized weakness for 1 month.
- Admission vitals: CBC – TLC: 530,000/μL, RBC 2 × 106/μL, hemoglobin 5.3 g/dL, platelet 90,000/μL.
Chest X-ray, liver function test, and serum electrolytes were all within normal limits. Markers for infectious disease were normal.
Bone marrow studies were positive for ALL and immunophenotyping confirmed ALL.
Two units of packed red cells was transfused. He underwent two leukapheresis procedures 48 h apart.
In the first procedure, inlet volume processed was 11835 ml, and total blood volume was 3588 ml. Postprocedure, the leukocyte count was 362,000/μL. Priming of the machine with one unit of matched PRBC was done, in view of significant anemia. Steroid administration was initiated due to severity of symptoms of leukostasis. Run time was 242 min; anticoagulant used was 989 ml.
A second procedure was done after 48 h. Inlet volume processed was 10039 ml. Run time was 220 min, and anticoagulant used was 837 ml. Pre- and post-procedure leukocyte counts were 226,000/μL and 155,000/μL, respectively [Table 2].
In all the procedures, the anticoagulant-to-blood ratio was maintained at 1:10. Adverse effects in the form of citrate toxicity or vasovagal reactions were not encountered during or after the procedure. Both the patients tolerated the procedure well without any complications.
Hydroxyurea 1 g thrice daily (decrease severity of symptoms) and allopurinol 300 ml once daily (prophylaxis for tumor lysis) were initiated for both patients, in addition to the supportive therapy for both the patients.
| Results|| |
The first patient had a 31.38% and 30.19% reduction in TLC after first and second procedures, respectively, with a cumulative reduction by 60.63%.
The second patient had a reduction in TLC of 31.7% and 31.41% after first and second procedures, respectively, with a cumulative reduction of 70%.
There was more than 30% reduction of leukocyte count in the first procedure itself and more than 60% reduction when both procedures were combined.
The decrease in white cell count consequent to leukapheresis enabled recovery of the patient from a life threatening situation to a stable condition permitting administration of normal chemotherapy protocols. Both patients subsequently underwent chemotherapy protocols and were stable before discharge.
| Discussion|| |
Hyperleukocytosis was first described by Freirich et al. and it has been reported that all patients with WBC counts greater than 200,000/μL or above showed either thrombi or cell aggregates.
Leukocytapheresis is indicated for hyperleukocytosis associated with leukostasis. A single 1–1.5 blood volume leukocytapheresis is expected to reduce the leukocyte count by 30%–60%.
Patients with hyperleukocytosis may present as a medical emergency requiring prompt recognition and initiation of therapy to prevent respiratory failure or intracranial hemorrhage.
Leukapheresis removes the circulating blasts quickly to alleviate the symptoms, whereas chemotherapy would take 24–48 h to achieve the same effect.
Therapeutic leukapheresis has also been used prophylactically to reduce the risk of tumor lysis syndrome, which may occur in patients with leukemia with high blast counts. In these patients, the initiation of chemotherapy leads to rapid cell death and hyperuricemia, resulting in acute renal failure.
All in all, besides the often critical overall condition of the patients with leukostasis, there have been no severe adverse events of leukocytapheresis published yet. Properly conducted, the treatment is well tolerated without major side effects.
Leukapheresis is known to be a generally safe procedure. According to the current knowledge, the following recommendations can be made:
Hyperleukocytosis in acute leukemia represents an emergent situation requiring appropriate therapy without any delay.
Early initiation of chemotherapy, hydroxyurea, and supportive care is fundamental and must be guaranteed.
Patients with symptoms of leukostasis should undergo leukocytapheresis in a timely manner. The treatment has to be performed in a center with experience in leukocytapheresis and emergency equipment. Leukocytapheresis procedures should be repeated daily until leukostatic symptoms have disappeared and WBC count has reached safe values. In asymptomatic patients with hyperleukocytosis, the decision for treatment remains at the discretion of the attending physician.
This work was supported by the Department of Transfusion Medicine and Department of Hematology/Hemato-Oncology of the Institute of Medical Sciences (IMS) and SUM Hospital, Bhubaneswar, Odisha, India, through equipment and supplies and staff members supporting the case
Financial support and sponsorship
Equipment and supplies provided by IMS and SUM Hospital, Bhubaneswar, Odisha, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Der-Cherng L, Ching-Hon P. Childhood acute lymphoblastic leukemia. In: Victor H, Daniel C, Edward GD, editors. Post Graduate Haematology. 5th
ed. Oxford: Blackwell Publishing; 2005. p. 542-60.
Jean H. Apheresis: Principles and Practice. In: McLeod BC, Price TH, Drew MJ, editors. Bethesda, MD: AABB Press; 1997. p. 251-61.
McKee LC Jr., Collins RD. Intravascular leukocyte thrombi and aggregates as a cause of morbidity and mortality in leukemia. Medicine (Baltimore) 1974;53:463-78.
Dutcher JP, Schiffer CA, Wiernik PH. Hyperleukocytosis in adult acute nonlymphocytic leukemia: Impact on remission rate and duration, and survival. J Clin Oncol 1987;5:1364-72.
Parra Salinas, I. M., González Rodriguez, V. P., & García-Erce, J. A. (2015). Therapeutic leukapheresis: 9-year experience in a University Hospital. Blood transfusion = Trasfusione del sangue, 13(1), 46-52. https://doi.org/10.2450/2014.0310-13
Pastore F, Pastore A, Whittmann G, Hiddemann W, Spikermann K. The role of therapeutic leukapheresis in hyperleucocytotic AML. PloS One 2014;9:e95062.
Tan D, Hwang W, Goh YT. Therapeutic leukapheresis in hyperleukocyticleukemias – The experience of a Tertiary Institution in Singapore. Ann Acad Med Singapore 2005;34:229-34.
Freireich EJ, Thomas LB, Frei E 3rd
, Fritz RD, Forkner CE Jr. A distinctive type of intracerebral haemorrhage associated with blast crisis in patients with leukemia. Cancer 1960;13:146-54.
Chekol SS, Bhatnagar B, Gojo I, Hess RJ. Leukapheresis for profound hyperleukocytosis. Transfus Apher Sci 2012;46:29-31.
Jean H. Principles and Practice. In: McLeod BC, Price TH, Drew MJ, editors. Bethesda, MD: AABB Press; 1997. p. 251-61.
Karren Q, Eugene MB. Introduction to therapeutic apheresis. In: Mc Leod BC, Price TH, Drew MJ, editors. Apheresis: Principles and Practice. Bethesda MD: AABB Press; 1997. p. 45-65.
Prentice AG, Donnelly JP. Supportive care in the management of leukemia. In: Victor H, Daniel C, Edward GD, editors. Post Graduate Hematology. 5th
ed. Oxford: Blackwell Publishing; 2005. p. 586-602.
Hölig K, Moog R. Leukocyte depletion by therapeutic leukocytapheresis in patients with leukemia. Transfus Med Hemother 2012;39:241-5.
Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukostasis and leukapheresis: Practice management. Blood Rev 2012;26:117-22.
[Table 1], [Table 2]