The effects of large-volume leukapheresis on hemoglobin,platelet and coagulation in patients with hyperleukocytic leukemia

Abstract

INTRODUCTION:

This study retrospectively analyzed a total of 86 leukapheresis treatments in 55 patients with hyperleukocytic leukemia (HLL).

METHODS:

In the leukapheresis treatments, the monitoring collection (MNC) program in COBE spectra continuous flow centrifuge (CFC) for blood component separator was used.

RESULTS:

In this study, the white blood cell (WBC) suspension volume collected in leukapheresis treatment were 870.72±208.40 mL, and significantly larger than that reported in previous study. Compared with before leukapheresis, there were no difference in patient with HLL on the peripheral blood platelet (PLT) count and hemoglobin (HGB) levels. The index plasma fibrinogen (FIB) concentration was slightly reduced by leukapheresis, however, it did not affect a lot the maintenance of normal hemostatic function in patients with HLL.

DISCUSSION:

Our data provided evidences that large-volume leukapheresis had no obvious effects on HGB level and coagulation functions in patient with HLL. So large-volume leukapheresis by CFC could be widely used in clinic.

Keywords

Leukapheresis hemoglobin platelet coagulation hyperleukocytic leukemia

1 Introduction

Leukemia mainly originates from the acquired early stage of malignant cloning hyperplasia pluripotent hematopoietic stem cells [1]. This malignancy is characterized by many leukemia cells that fail to undergo differentiation and maturation but stack in the bone marrow [2]. After a lot of immature leukemia cells enter the blood stream, they can easily infiltrate organs and tissues, leading to organs embolism, dysfunction of coagulation [3]. Hyperleukocytosis is usually defined by a WBC count > 100×10⁹/L, which is accompanied by symptoms of leukostasis or hyperviscosity [4, 5]. Furthermore, due to the adhesive behaviour of leukocytes, hyperleukocytosis will increase blood viscosity, which in turn lead to thrombus formation especially in the microcirculation [6, 7].

To minimize the tissue damages caused by the leukemia cells, when WBC count is more than 100×10⁹/L, the blood component separator should be used urgently to perform leukapheresis therapy [8]. Leukapheresis has been used for leukoreduction in leukemia patients with hyperleukocytosis [4, 9]. Leukapheresis has been proposed to quickly decrease the WBC count and improve survival in patients with hyperleukocytosis. Although superior efficiency of leukapheresis in abating WBC counts, its use remains controversial. There are two kinds of blood component separators available for leukapheresis therapy, CFC and intermittent flow centrifuge leukapheresis. However, there are limited reports on the evaluation of these two blood component separator systems for leukapheresis. Moreover, there are no clinical guidelines for its application. There is also lack of uniform standards for the leukocyte amount collected in a single treatment. Previous study reported that the volume of WBC suspensions collected in a single depletion therapy is generally 500 mL, and more than 6 leukapheresis treatments are necessary for the hyperleukocytosis [9]. To improve the efficiency of leukapheresis therapy, in this study we used the COBE spectra CFC for blood component separator to perform large-volume leukapheresis. The blood volumes [20–25% of total blood volume, (870.72±208.40) mL] in our large-volume leukapheresis treatment were significantly larger than that reported in previous study. Here, we retrospectively analyzed a total of 86 large-volume leukapheresis treatments in 55 patients with HLL. We showed the peripheral blood WBC count, platelet count, HGB levels and plasma FIB concentration were significantly reduced in all patients treated with leukapheresis. Although FIB concentration was reduced, it did not affect the maintenance of normal hemostatic function. Our study suggested large-volume leukapheresis by CFC can be widely used in clinic.

2 Materials and methods

2.1 Patients and materials

Fifty-five patients with HLL received the leukapheresis therapy in the First Affiliated Hospital of Zhengzhou University between February 2008 and June 2016.

2.2 Statistical analysis

All the data collected were analyzed with SAS 9.0 and SPSS 17.0 statistical software. Data were analyzed using one-way ANOVA test. The statistical significance was set at a level of P < 0.05.

3 Results

3.1 Cell components detection values in pre-leukapheresis and loss values in post-leukapheresis

Each leukapheresis treatment took 236.59±27.89 min to circulate 12101.59±1984.67 mL blood. The volumes of acid citrate dextrose-A (ACD-A) preservative solution were 680 to 1567 mL (980.89±174.22 mL). Of these 55 HLL patients aged 39.42±14.96 years (ranging from 14 to 80 years old), 41 were males and 14 were females, including 5 cases with acute lymphoblastic leukemia (ALL), 28 cases with acute non-lyphoblastic leukemia (ANLL) and 22 cases with chronic myeloid leukemia (CML). The TBV of patients were 2540 to 5622 mL (4187.45±657.48 mL) automatically calculated by the COBE Spectra CFC blood component separator (GAMBRO BCT, USA) according to the patients’gender, height and weight. The WBC suspension volumes collected from patients were 496–1368 mL (870.72±208.40). A total of 86 leukapheresis treatments were included in this study. In 86 leukapheresis treatments, the volumes of input liquid (ACD-A volumes + 10% calcium gluconate injection + 0.9% sodium chloride) were greater than the volumes of output liquid (WBC suspension volumes). These 84 leukapheresis treatments were defined as positive balance. Conversely, in another 2 leukapheresis treatments, the volumes of input liquid were less than the volumes of output liquid. These two leukapheresis treatments were defined as negative balance. In all the treatments, the ratios of the altered liquid volumes to patients’ total blood volumes (TBV) were 9.83±5.02%. I.e. (the volumes of input liquid - WBC suspension volumes) / TBV×100% = the ratios of the altered liquid volumes.

As shown in Table 1, in comparison of peripheral blood WBC count between pre-leukapheresis and post-leukapheresis, peripheral blood WBC counts were 207.36×10⁹/L and 123.85×10⁹/L, respectively. The decline value of WBC was 83.51×10⁹/L in the patients treated by leukapheresis. PLT contents were 92.19×10⁹/L and 80.38×10⁹/L in pre-leukapheresis and post-leukapheresis, respectively. HGB contents were 80.31 g/L and 85.54 g/L in pre-leukapheresis and post-leukapheresis, respectively. Activated partial thromboplastin time (APTT) contents were 37.91 sec and 38.67 sec in pre-leukapheresis and post-leukapheresis, respectively. Fibrinogen concentration was 2.72 sec and 2.18 sec in pre-leukapheresis and post-leukapheresis, respectively. Thrombin time (TT) contents were 18.31 sec and 17.52 sec in pre-leukapheresis and post-leukapheresis, respectively. Creatinine (Cr) contents were 75.79μmol/L and 79.24μmol/L in pre-leukapheresis and post-leukapheresis, respectively. Creatine kinase (Ck) contents were 83.44 U/L and 82.51 U/L in pre-leukapheresis and post-leukapheresis, respectively. Lactate dehydrogenase (LDH) contents were 127.53 U/L and 104.46 U/L in pre-leukapheresis and post-leukapheresis, respectively. Above results suggested that the peripheral blood WBC count and FIB concentration was reduced in patients treated with leukapheresis (P < 0.001). The levels of PLT, HGB, HCT, APTT, TT, Cr and Ck were no change(P > 0.05). The level of LDH subtle changed in post-leukapheresis (P < 0.05).

Table 1
Cell components detection valve of pre-leukapheresis and post-leukapheresis

Groups Pre-leukapheresis Post-leukapheresis P value

WBC (×10⁹/L) 207.36 123.85 <0.001

PLT (×10⁹/L) 92.19 80.38 >0.05

HGB (g/L) 80.31 85.54 >0.05

HCT 26.67 24.92 >0.05

APTT (sec) 37.91 38.67 >0.05

FIB (sec) 2.72 2.18 <0.001

TT (sec) 18.31 17.52 >0.05

Cr (μmol/L) 75.79 79.24 >0.05

Ck (U/L) 83.44 82.51 >0.05

LDH (U/L) 127.53 104.46 <0.05

Groups	Pre-leukapheresis	Post-leukapheresis	P value
WBC (×10⁹/L)	207.36	123.85	<0.001
PLT (×10⁹/L)	92.19	80.38	>0.05
HGB (g/L)	80.31	85.54	>0.05
HCT	26.67	24.92	>0.05
APTT (sec)	37.91	38.67	>0.05
FIB (sec)	2.72	2.18	<0.001
TT (sec)	18.31	17.52	>0.05
Cr (μmol/L)	75.79	79.24	>0.05
Ck (U/L)	83.44	82.51	>0.05
LDH (U/L)	127.53	104.46	<0.05

4 Discussion

Excessive WBC proliferation is the major reason leading to leukostasis in HLL patients. Leukapheresis used for treatment of HLL patients can reduce the number of WBC cells quickly and effectively and prevent hyperviscosity, leukostasis and tumor lysis syndrome (TLS) [8]. Leukapheresis has been used as supplementation of chemotherapy in HLL patients and demonstrated the suitability for wide clinical applications.

Fig. 1

Parameter changes before and after treatment. legend: blue –decline; red - increase.

The purpose of leukapheresis is to reduce the count of malignant leukocytes in HLL patients. Therapeutic effect of leukapheresis depends on the amount of WBCs collected. However, there is still lack of universal standards on how to determine the number of WBCs collected in each treatment and the effectiveness of treatment. Recent studies reported that the volume of WBC suspension collected is about 500 mL, and the total number of WBCs collected is up to 300×10⁹ by either intermittent flow centrifuge or CFC blood component separator in each treatment. In this study, the blood volumes in our large-volume leukapheresis treatment were (870.72±208.40) mL (20–25% of TBV), and significantly larger than that reported in a previous study.

Abnormal WBC from HLL patients is shown not only in blood circulation but also to be deposited in the spleen and other storage pools. When the WBC of peripheral blood is depleted after leukapheresis, the WBC deposited in storage pools enters into blood circulation. Therefore, the decline value and rate of WBC in peripheral blood cannot be evaluated for the collection effect of leukapheresis alone. It is reasonable that the total count of depleted WBCs, or the depleted value and rate of WBC were used to evaluate the collection effect.

The monitoring collection (MNC) program of COBE Spectra CFC for blood component separator used in this study had shown improvement of the efficiency of leukapheresis in 55 HLL patients. Although the WBC suspension collected was 20–25% volume of TBV, the liquid input volume was more than the WBC suspension in the whole course of treatment. There was only 150 mL blood in extracorporeal circulation in the process of the MNC program of COBE Spectra CFC for blood component separator, so that the anticoagulant (ACD-A blood preservative solution) volume used for leukapheresis was usually more than the volume of WBC suspension collected. The injection of 263 mL 0.9% sodium chloride was applied for the process of backwash when the MNC program was ended, ensuring the relative stability of the patients’ hemodynamics. There was no obvious manifestation of hypovolemia occurring during leukapheresis and within 1 hour after leukapheresis therapy in the high proportion of leukapheresis in 55 HLL patients.

Since some amount of plasma might be lost during the collection of WBC suspension, it was thus important to increase the volume of blood circulated and WBCs suspension. In addition, the leukapheresis therapy possibly affects anticoagulation of HLL patients. It was thus necessary to evaluate the safety of treatment. In this study, large-volume leukapheresis declined HGB level only by 5.25 g/L on average; it was thus no severe adverse effect on the patients. In addition, we found that there was no significant difference for PT, APTT and TT between pre- and post-leukapheresis. Although FIB concentration was reduced after leukapheresis, it did not affect the maintenance of normal hemostatic function. These results were consistent with previous reports that the activity of main coagulation factors to maintain normal hemostatic function is not affected significantly in leukemia patients whose liver functioned is not significantly impaired.

5 Conclusion

Taken together, the high proportion (20–25% of TBV) of leukapheresis with the CFC blood component separator for treatment of HLL patients could significantly reduce the number of leukemia cells; while patients may lose some RBCs, platelets, HGB and coagulation component, such losses are limited to the scope of compensation in the body and will not apparently affect the therapeutic effect of leukapheresis.

Abbreviations

WBC: white blood cell; HGB: hemoglobin; PLT: platelet; HLL: hyperleukocytic leukemia; MNC: monitoring collection; CFC: continuous flow centrifuge; TBV: total blood volume; FIB: fibrinogen; PT: prothrombin time; APTT: activated partial thromboplastin time; TT: thrombin time; FIB: plasma fibrinogen; FDP: fibrin degradation products; DIC: disseminated intravascular coagulation; TLS: tumor lysis syndrome; RBC: red blood cells; ALL: acute lymphoblastic leukemia; ANLL: acute non-lyphoblastic leukemia; CLL: chronic lymphocytic leukemia; CML: chronic myeloid leukemia; ECG: electrocardioscope monitor; IRB: Institutional Review Board; ACD-A: acid citrate dextrose-A; Cr: Creatinine; Ck: Creatine kinase; LDH: Lactate dehydrogenase

Author contributions

Lin Chen and Xiangfu Liu designed the study; Lingling Liu and Caihan Zhao carried out the data extraction; Lin Chen, Qing Yuan, Ruifang Fan, Qing Tang and Wei Du analyzed the data; Qing Yuan, Lin Chen and Lingling Liu made the tables; Lingling Liu, Qing Yuan and Xiangfu Liu drafted the paper; all authors revised the paper; all authors approved the final version of the manuscript.

Conflict of interest

None.

Footnotes

Acknowledgments

Not applicable.

Statement of ethics

This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University and all aspects of the study complied with the Declaration of Helsinki. IRB approved number: 20150322.

Funding

This work was supported by National Natural Science Foundation of China, Grant/Award Number: 81974004.

Data availability statement

None.

The supplementary material is available in the electronic version of this article: .

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