Leukapheresis and Hyperleukocytosis, Past and Future

Figures & data

Figure 1 The emergence of different blood cell separators at different periods.

Abbreviations: NCI-IBM, the National Cancer Institute and the International Business Machines Corporation; FL, filtration leukapheresis.

Table 1 Indication Categories for Therapeutic Leukapheresis

Disease Name	Modality	Disease Condition	Treatment Status	Recommendation
Hyperleukocytosis	Leukapheresis	Symptomatic	Second-line	Moderate
		Prophylaxis or secondary	Individualization	Weak
Inflammatory bowel disease	Adsorptive cytapheresis	Ulcerative colitis	Individualization	Strong
		Crohn’s disease	Individualization	Weak

Table 2 The Pros and Cons of Leukapheresis

Author and Year	Advantage	Disadvantage	Perspectives
Powell et al (1991)^Citation35	Leukapheresis could modulate the cell cycle distribution and increase the fraction of leukemia cells in S-phase.	NA	Leukapheresis may increase the efficiency of cytarabine and other S-phase specific agents.
Galera et al (2016)^Citation39	Leukapheresis could improve pulmonary leukostasis in pregnant woman without side effect.	NA	Leukapheresis was recommended for the treatment of hyperleukocytosis with neurologic and pulmonary manifestation by ASFA as it could reduce the intravascular leukemic cellular burden rapidly and improve tissue perfusion.
Bruserud et al (2012)^Citation36	Leukapheresis was a safe and effective procedure for the treatment of hyperleukocytic leukemia with life-threatening complications and without side effect.	NA	Leukapheresis may have therapeutic effect in hyperleukocytic leukemia patients with leukostasis. The important thing to note was chemotherapy should not be postponed for the prevention of the rapid re-accumulation of blasts.
Sung et al (2012)^Citation37 Jin et al (2018)^Citation34	Leukapheresis could reduce the occurrence of renal failure and metabolic derangements with little toxicity on hepatic-renal function	NA	Leukapheresis was safe and efficient in leukoreduction and could be used for the treatment of children and pregnant women with hyperleukocytic leukemia.
Giammarco et al (2017)^Citation42	NA	Leukapheresis required specialized equipment and trained personnel.	It may be challenging to perform leukapheresis on large-scale.
Allon et al (2007)^Citation43	NA	Leukapheresis required a central venous catheter which hold a high risk of bleeding, thrombosis and catheter-related infection and venous stenosis at the catheter site.	Patients who underwent the treatment of leukapheresis need more intensive care.
Punzel et al (2017)^Citation46	NA	Leukapheresis can reduce the number of leukocytes rapidly along with the loss of red blood cell and platelet	Patients who underwent leukapheresis with hemoglobin below 60 g/L or platelet below 30×10^9/L need be pre-treated with red blood cell or platelet transfusion.
Sanz et al (2009)^Citation47	NA	leukapheresis may exacerbate coagulopathy associate with a high risk of death at induction.	Leukapheresis was not recommended for the treatment of acute promyelocytic leukemia.

Abbreviation: NA, not available.

Table 3 A Summary of Clinical Studies of Leukapheresis in Patients with Hyperleukocytic Leukemia

Author and Year	Patients	Leukoreduction Rate	Study Summary	P value
Porcu et al (1997)^Citation49	48	> 50%	Leukapheresis could not improve one-week mortality in patients with hyperleukocytic leukemia, especially these presented with renal, neurological and respiratory complications.	>0.200
Thiebaut et al (2000)^Citation50	53	Median was 50% (range 0 to 91)	Patients with hyperleukocytic leukemia may benefit from initial leukapheresis.	NA
Giles et al (2001)^Citation51	71	Median was nearly 57% (66.4/116.5)	Leukapheresis could reduce two-week mortality and achieved a higher complete remission rate compared to control group.	0.060
Chang et al (2007)^Citation52	22	Not shown	Leukapheresis could not improve early mortality, on the contrary, may be detrimental.	0.367
Bug et al (2007)^Citation56	25	Median was 47%	Leukapheresis could reduce the risk of early death by Day-21, but had no impact on overall survival.	0.015
Oberoi et al (2014)^Citation8	1354	Not shown	Leukapheresis did not reduce early mortality in patients with hyperleukocytic leukemia.	0.670
Wong et al (2015)^Citation55	31	Median was nearly 69%	Leukapheresis could not improve 30-day mortality and overall survival.	0.250
Nan et al (2017)^Citation54	26	Median was 55% (range19 to 94)	Leukapheresis was associated with significantly lower 28-day mortality rate compared to control group.	0.022
Choi et al (2018)^Citation53	59	Median was nearly 59% (119/202)	There was not enough evidence to show that leukapheresis had a positive effect on survival outcome and incidence of early complications.	AML: 0.846 ALL: 0.822
Stahl et al (2020)^Citation58	113	Not shown	Leukapheresis had no impact on 30-day mortality, achievement of complete remission, or overall survival.	0.329

Abbreviation: NA, not available.

Figure 2 The indication and therapeutic strategy of leukapheresis in the treatment of hyperleukocytosis.

Powell BL, Gregory BW, Evans JK, et al. Leukapheresis induced changes in cell cycle distribution and nucleoside transporters in patients with untreated acute myeloid leukemia. Leukemia. 1991;5(12):1037–1042.

 PubMed Web of Science ®Google Scholar

Galera P, Haynes S, Sulmasy P, et al. Physiological measurements corroborate symptomatic improvement after therapeutic leukapheresis in a pregnant woman with chronic myelogenous leukemia. J Clin Apher. 2016;31(4):393–397. doi:10.1002/jca.21410

 PubMed Web of Science ®Google Scholar

Bruserud Ø, Liseth K, Stamnesfet S, et al. Hyperleukocytosis and leukocytapheresis in acute leukaemias: experience from a single centre and review of the literature of leukocytapheresis in acute myeloid leukaemia. Transfusion Med. 2013;23(6):397–406. doi:10.1111/tme.12067

 PubMed Web of Science ®Google Scholar

Sung L, Aplenc R, Alonzo TA, Gerbing RB, Gamis AS. Predictors and short-term outcomes of hyperleukocytosis in children with acute myeloid leukemia: a report from the Children’s Oncology Group. Haematologica. 2012;97(11):1770–1773. doi:10.3324/haematol.2012.065490

 PubMed Web of Science ®Google Scholar

Jin Y, Guo S, Cui Q, et al. A hospital based retrospective study of factors influencing therapeutic leukapheresis in patients presenting with hyperleukocytic leukaemia. Sci Rep. 2018;8(1):294. doi:10.1038/s41598-017-17534-4

 PubMed Web of Science ®Google Scholar

Giammarco S, Chiusolo P, Piccirillo N, et al. Hyperleukocytosis and leukostasis: management of a medical emergency. Expert Rev Hematol. 2017;10(2):147–154. doi:10.1080/17474086.2017.1270754

 PubMed Web of Science ®Google Scholar

Allon M. Current management of vascular access. Clin J Am Soc Nephrol. 2007;2(4):786–800. doi:10.2215/CJN.00860207

 PubMed Web of Science ®Google Scholar

Punzel M, Kozlova A, Quade A, Schmidt AH, Smith R. Evolution of MNC and lymphocyte collection settings employing different Spectra Optia(®) Leukapheresis systems. Vox Sang. 2017;112(6):586–594. doi:10.1111/vox.12540

 PubMed Web of Science ®Google Scholar

Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875–1891. doi:10.1182/blood-2008-04-150250

 PubMed Web of Science ®Google Scholar

Porcu P, Danielson CF, Orazi A, Heerema NA, Gabig TG, McCarthy LJ. Therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate. Br J Haematol. 1997;98(2):433–436. doi:10.1046/j.1365-2141.1997.1943011.x

 PubMed Web of Science ®Google Scholar

Thiébaut A, Thomas X, Belhabri A, Anglaret B, Archimbaud E. Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis. Ann Hematol. 2000;79(9):501–506. doi:10.1007/s002770000162

 PubMed Web of Science ®Google Scholar

Giles FJ, Shen Y, Kantarjian HM, et al. Leukapheresis reduces early mortality in patients with acute myeloid leukemia with high white cell counts but does not improve long- term survival. Leuk Lymphoma. 2001;42(1–2):67–73. doi:10.3109/10428190109097677

 PubMed Web of Science ®Google Scholar

Chang MC, Chen TY, Tang JL, et al. Leukapheresis and cranial irradiation in patients with hyperleukocytic acute myeloid leukemia: no impact on early mortality and intracranial hemorrhage. Am J Hematol. 2007;82(11):976–980. doi:10.1002/ajh.20939

 PubMed Web of Science ®Google Scholar

Bug G, Anargyrou K, Tonn T, et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. Transfusion. 2007;47(10):1843–1850. doi:10.1111/j.1537-2995.2007.01406.x

 PubMed Web of Science ®Google Scholar

Oberoi S, Lehrnbecher T, Phillips B, et al. Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis. Leuk Res. 2014;38(4):460–468. doi:10.1016/j.leukres.2014.01.004

 PubMed Web of Science ®Google Scholar

Wong GC. Hyperleukocytosis in acute myeloid leukemia patients is associated with high 30-day mortality which is not improved with leukapheresis. Ann Hematol. 2015;94(12):2067–2068. doi:10.1007/s00277-015-2472-2

 PubMed Web of Science ®Google Scholar

Nan X, Qin Q, Gentille C, et al. Leukapheresis reduces 4-week mortality in acute myeloid leukemia patients with hyperleukocytosis - a retrospective study from a tertiary center. Leuk Lymphoma. 2017;58(9):1–11. doi:10.1080/10428194.2016.1277386

 PubMed Web of Science ®Google Scholar

Choi MH, Choe YH, Park Y, et al. The effect of therapeutic leukapheresis on early complications and outcomes in patients with acute leukemia and hyperleukocytosis: a propensity score-matched study. Transfusion. 2018;58(1):208–216. doi:10.1111/trf.14329

 PubMed Web of Science ®Google Scholar

Stahl M, Shallis RM, Wei W, et al. Management of hyperleukocytosis and impact of leukapheresis among patients with acute myeloid leukemia (AML) on short- and long-term clinical outcomes: a large, retrospective, multicenter, international study. Leukemia. 2020;34(12):3149–3160. doi:10.1038/s41375-020-0783-3

 PubMed Web of Science ®Google Scholar