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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 6  |  Issue : 1  |  Page : 106-109

A case report of apheresis granulocyte concentrates and the whole blood-derived pooled buffy coat transfusions in a neutropenic hematopoietic stem cell transplant recipient


Department of Transfusion Medicine, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission21-Sep-2020
Date of Decision01-Mar-2021
Date of Acceptance18-Mar-2021
Date of Web Publication29-May-2021

Correspondence Address:
Dr. Shashank Ojha
Department of Transfusion Medicine, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_97_20

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  Abstract 


Granulocytes may be procured either as apheresis granulocyte concentrate (AGC) or as a pooled buffy coat granulocytes (PBCG) derived from whole blood donations. The chronic myelomonocytic leukemia patient with active pneumocystis pneumonia infection, received two transfusions of AGC and PBCG each, for prolonged severe neutropenia. AGCs had a higher mean white blood cells count per bag (1.63 × 1010 vs. 1.53 × 1010), neutrophil count per bag (1.05 × 1010 vs. 0.76 × 1010), and mean neutrophils percentage (62.45% vs. 49.25%), whereas PBCGs had a higher mean red blood cells volume per bag (196.1 vs. 62.5 ml) and platelet counts (5.03 × 1011 vs. 3.6 × 1011). The rise in patients' absolute neutrophil count was comparable with both AGC and PBCG transfusions. Granulocyte transfusions helped in the management of an acute neutropenic crisis. Whole blood-derived PBCGs may be a viable alternative in to AGCs. PBCGs have a lot of logistic issues and each blood center should have its standard operating procedure.

Keywords: Apheresis, buffy coat, granulocytes, neutropenia, pooling


How to cite this article:
Gupta AM, Ojha S, Sumathi S H, Poojary M. A case report of apheresis granulocyte concentrates and the whole blood-derived pooled buffy coat transfusions in a neutropenic hematopoietic stem cell transplant recipient. Glob J Transfus Med 2021;6:106-9

How to cite this URL:
Gupta AM, Ojha S, Sumathi S H, Poojary M. A case report of apheresis granulocyte concentrates and the whole blood-derived pooled buffy coat transfusions in a neutropenic hematopoietic stem cell transplant recipient. Glob J Transfus Med [serial online] 2021 [cited 2021 Dec 7];6:106-9. Available from: https://www.gjtmonline.com/text.asp?2021/6/1/106/317181




  Introduction Top


Even in the modern era of newer antimicrobials and the use of hematopoietic growth factors to reduce the duration of posttreatment neutropenia, infection remains a major cause of morbidity and mortality in high-dose chemotherapy regimens and hematopoietic stem cell transplantation (HSCT) patients.[1]

Logistic difficulties in supplying apheresis granulocytes concentrate (AGC) like donor availability and donor mobilization (granulocyte colony-stimulating factor and steroids) are well acknowledged. The alternative source of granulocytes, derived from whole blood donations, may be easily available as a by-product of blood component separation. In vitro tests have demonstrated that the neutrophil function of pooled buffy coat granulocytes (PBCG) was well preserved during the 24 h storage.[2],[3],[4]


  Case Report Top


Our patient was a 36-year-old male, allogeneic HSCT recipient with the diagnosis of chronic myelomonocytic leukemia. The patient had clinically fungal pneumonia, active pneumocystis pneumonia infection and was treated with granulocyte infusions.

Method of pooled buffy coat granulocytes preparation

The process of PBCG preparation is depicted in [Figure 1]. Red cell reduction was not performed as the patient was also having severe anemia. AGC/PBCGs viability was performed by the trypan blue dye exclusion method.[5]
Figure 1: Schematic flow diagram for the pooled buffy coat granulocyte concentrates

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Patients' course in hospital

The patient received two transfusions of AGC on day +3 and day +6 post-HSCT on account of persistent neutropenia (ANC <0.5 × 109/L). Both the AGCs were collected on Spectra Optia (Terumo BCT, Lakewood, USA) after granulocyte colony-stimulating factor (G-CSF) (10 μg/kg) and dexamethasone (8–12 mg) mobilization but without hydroxyethyl starch as a sedimenting agent. As the patient continued to have severe neutropenia and no apheresis donors were available, PBCGs were decided to be transfused. PBCGs were transfused on day +11 and day +18, post-HSCT. Individual AGC and PBCG product values are summarized in [Table 1]. Changes in patient's hematological parameters after AGCs and PBCGs transfusions are shown in [Table 2]. AGCs had a higher mean white blood cells (WBC) count per bag (1.63 × 1010 vs. 1.53 × 1010), neutrophil count per bag (1.05 × 1010 vs. 0.76 × 1010), and mean neutrophils percentage (62.45% vs. 49.25%) in comparison to PBCG, whereas PBCGs had a higher mean red blood cells volume per bag (196.1 ml vs. 62.5 ml) and platelet counts (5.03 × 1011 vs. 3.6 × 1011) in comparison to AGC. All the transfusion events were uneventful. As per the DGHS Transfusion Medicine Technical Manual, every granulocyte component must contain at least 1 × 1010 granulocytes and one of the AGC and both PBCGs did not fulfill this criteria but were transfused in view of the dire need.[6]
Table 1: Quality control parameters of different granulocyte products

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Table 2: Patient's hematological parameters pre-and post (at 1 h and 24 h) apheresis granulocyte concentrate/pooled buffy coat granulocyte transfusion

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Patient outcome

The rise in patients' absolute neutrophil count was insufficient but comparable with both AGCs and PBCGs transfusions. Granulocyte transfusions (GTX) helped in the management of an acute neutropenic crisis.


  Discussion Top


PBCGs are still an unexplored territory in India. Many times, physicians request the GTX on an emergency basis and the cross-match compatible apheresis donor may not be available. Blood centers must have all the standard operating procedures in place for any form of granulocyte preparations in such emergencies.

The shelf life of pooled buffy coat granulocytes

Despite the preservation of functional activities, the total WBC counts of granulocyte concentrate decreases 24 h after storage.[7] Hence, PBCGs should be transfused as early as possible. The preparation of PBCGs may take a longer duration for its preparation but it may still be effective.

Ethical consideration of granulocyte colony-stimulating factor/steroids and hydroxyethyl starch to donors

The UK Transfusion Services do not permit the administration of G-CSF and steroids to volunteer, unrelated donors.[8] The recent RING trial suggested that patients receiving ≥0.6 × 109 granulocytes/kg/transfusion tended to have better clinical outcomes.[9]

Disadvantages of pooled buffy coat granulocytes

On average, a single buffy coat had a neutrophil count of 0.1 × 1010 per bag and to get the least adequate dose, at least 10 buffy coats must be pooled.[2],[3],[4]>/sup> The RING trial suggested that the effective adult dose should be at least 4 × 1010.[9] Alloimmunization is a possible threat due to large donor exposures.[3] Moreover, a higher dose of granulocytes was not possible with PBCGs.

Logistic issues with pooled buffy coat granulocytes

After the blood donation, the component separation, blood grouping, with TTI testing takes a great deal of time. After the results, cross-match, pooling, gamma irradiation, and quality control will take extra time. Hence, the PBCG transfusion may happen, 8–12 h after the collection of the first blood unit. Overall, it will still take a shorter time to pool buffy coats as compared to select, mobilize and do the apheresis procedure on a donor.

The dilemma of granulocyte transfusions

The recent randomized controlled “RING” trial also did not show any survival benefits of GTX.[9] However, it had a low accrual rate, and the required statistical significance may not have reached due to the lower power of the study. GTX may be beneficial in countries like India, where neutropenic patients have a very high incidence of infection and multidrug-resistant organisms are common.[10] Hence, the need and effectiveness of GTX should be decided on an individual patient basis.


  Conclusions Top


High-dose AGCs are the product of choice for neutropenic patients. Whole blood-derived PBCGs may be a viable alternative to AGCs when the same are not available. PBCGs have a lot of logistic issues and each blood center should have its standard operating procedures. The efficacy of GTX is still uncertain and further research is required in this field.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Drewniak A, Kuijpers TW. Granulocyte transfusion therapy: Randomization after all? Haematologica 2009;94:1644-8.  Back to cited text no. 1
    
2.
Bashir S, Stanworth S, Massey E, Goddard F, Cardigan R. Neutrophil function is preserved in a pooled granulocyte component prepared from whole blood donations. Br J Haematol 2008;140:701-11.  Back to cited text no. 2
    
3.
Massey E, Harding K, Kahan BC, Llewelyn C, Wynn R, Moppett J, et al. The granulocytes in neutropenia 1 (GIN 1) study: A safety study of granulocytes collected from whole blood and stored in additive solution and plasma. Transfus Med 2012;22:277-84.  Back to cited text no. 3
    
4.
van de Geer A, Gazendam RP, Tool AT, van Hamme JL, de Korte D, Van den Berg TK, et al. Characterization of buffy coat-derived granulocytes for clinical use: A comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products. Vox Sang 2017;112:173-82.  Back to cited text no. 4
    
5.
Strober W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol 2015;111:A3.B.1-3.  Back to cited text no. 5
    
6.
Saran RK, editor. Transfusion Medicine Technical Manual. New Delhi: Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India; 2003. p. 355.  Back to cited text no. 6
    
7.
Drewniak A, Boelens JJ, Vrielink H, Tool AT, Bruin MC, van den Heuvel-Eibrink M, et al. Granulocyte concentrates: Prolonged functional capacity during storage in the presence of phenotypic changes. Haematologica 2008;93:1058-67.  Back to cited text no. 7
    
8.
Joint UKBTS Professional Advisory Committee, Position Statement Granulocyte Therapy; November, 2017. Available from: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/14874/inf2764-clinical-guidelines-for-the-use-of-granulocyte-transfusions.pdf. [Last accessed on 2020 Sep 21].  Back to cited text no. 8
    
9.
Price TH, Boeckh M, Harrison RW, Mc Cullough J, Ness PM, Strauss RG, et al. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood 2015;126:2153-61.  Back to cited text no. 9
    
10.
Garg A, Gupta A, Mishra A, Singh M, Yadav S, Nityanand S. Role of granulocyte transfusions in combating life-threatening infections in patients with severe neutropenia: Experience from a tertiary care centre in North India. PLoS One 2018;13:e0209832.  Back to cited text no. 10
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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