| Abstract|| |
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment modality for a range of hematological disorders including malignancies. The increasing volumes of HSCTs impact transfusion services and the requirement of blood products vary depending on the primary disease, type and phase of transplant, and the HSCT donor type.
MATERIALS AND METHODS: This study analyzed the factors affecting blood component requirements in patients undergoing HSCT. The authors studied the transfusion requirement of packed red blood cells (PRBC) and platelets (PLT) up to 100 days post-transplant among 617 adult patients undergoing HSCT during the study period (2007–2019).
RESULTS: Requirement of PRBC and PLT was significantly higher (P < 0.05) in allogenic HSCT cases across all three phases of transplant compared to autologous HSCT. Unlike PRBC requirement, the PLT requirement was significantly higher during peri-transplant period for haploidentical HSCT and major ABO-incompatible HSCT group compared to matched related donor HSCT and ABO identical HSCT, respectively. In subset analysis based on diagnosis with leukemia as reference, the multiple myeloma group required less while the anemia group required more PRBC and PLT transfusions. The leukemia group required more PRBC than lymphoma group, while the PLT requirement was vice-versa.
CONCLUSION: Factors such as allogeneic HSCT, haploidentical donor type, major ABO-incompatible HSCT, and primary diagnosis as leukemia or anemia were the predictors for increased need of blood products. As higher transfusion requirements may translate into increased costs of treatment, a study like this can help in managing blood component inventory and planning treatment costs of a HSCT program.
Keywords: ABO compatible, allogeneic, autologous, blood utilization, haploidentical, stem cell transplantation
|How to cite this URL:|
Ojha S, Patle V, Nagaraju P, Khattry N. Blood components utilization in hematopoietic stem cell transplantation: Thirteen-year analysis from an apex oncology center of India. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356852
| Introduction|| |
Hematopoietic stem cell transplantation (HSCT) as a treatment modality has proven to be potentially curative for a range of hematological disorders including malignancies. HSCT has also been tried for nonhematological malignancies with limited number of indications. The traditional conditioning regimens for HSCTs have been myeloablative, with disease eradication and host immunosuppression (for allograft acceptance) being their key considerations towards achieving favorable outcomes. However, as more knowledge has been gained in the field of HSCT and with expanding number of indications, the newer regimens being used are mostly nonmyeloablative. The use of reduced intensity conditioning (RIC) regimen or nonmyeloablative regimens has led to a reduction in morbidity, complications and mortality traditionally associated with myeloablative regimens. The change of regimen has also allowed expansion of application of HSCT to older patients and to those with comorbidities. Myeloablative or high dose conditioning regimens use cyclophosphamide and total body irradiation (TBI) or cyclophosphamide/TBI and etoposide or busulfan/cyclophosphamide. RIC regimens use TBI with or without fludarabine, or cyclophosphamide with or without anti-thymocyte globulin.
Providing transfusion support in HSCT can be quite challenging and demanding. There is a limited published data on the variance in packed red blood cell (PRBC) and platelet (PLT) requirement across HSCT modality in consideration to factors such as primary diagnosis, type of transplant, stem cell donor type, ABO compatibility, and complications.,,,, There are various reports citing differential transfusion requirement across types of regimens. Reduced transfusion requirements have been reported in cases with RIC/nonmyeloablative regimens as compared to myeloablative regimens. Apart from the regimens, the transfusion requirement varies depending on complications of HSCT like pure red cell aplasia, acute or chronic graft versus host disease (GvHD), passenger lymphocyte syndrome, autoimmune hemolytic anemia, veno-occlusive disease. The requirement of transfusion also varies with the type of HSCT donor with differential requirements in autologous HSCT and allogenic HSCT. Among allogenic HSCT, higher transfusion requirement have been reported in haplo-identical and HLA matched unrelated HSCTs compared to HLA-matched related donor HSCT., ABO incompatibility though not a barrier to perform HSCT can affect transfusion requirement. ABO incompatible HSCTs have been reported to require more transfusion support.
Most of the published information is from centers in developed countries.,, Whereas in countries like India, there has been a steady rise in number of HSCTs being performed. However, barring one study, the data on transfusion requirement in HSCT patients from India is not available. This study attempts to analyze the transfusion requirement (PRBC and PLT) up to 100 days post HSCT in adult patients undergoing treatment at Western India's high volume transplant center. Our data may be used for planning individualized transfusion support and better blood component inventory management in a high volume center.
| Materials and Methods|| |
This is a retrospective observational study of a cohort of 617 adult patients who underwent HSCT over a period of 13 years from January 1, 2007, to December 31, 2019. We analyzed the median requirement of blood components, mainly PRBC and PLT, across different subset of HSCT patients classified on the basis of primary disease (leukemia, lymphoma, myeloma, anemia), type of transplant (autologous, allogenic), stem cell donor type (matched related/unrelated, haploidentical) and ABO incompatibility between recipient-donor pair (major, minor, bidirectional).
Patients and donor
Patient data retrieved from electronic and physical medical records maintained in the hospital information system and departmental record room. Records of all consecutive adult patients (≥16 years of age) undergoing HSCT at our center were evaluated for blood component utilization during three phases of transplant. For simplicity of data analysis, the study team defined the three phases. Pretransplant phase considered from the time of diagnosis until the start of conditioning regimen. Peri-transplant phase ranged from the day of start of conditioning regimen (days counted in minus i.e., −7, −6, etc.,) till the day of engraftment (day + 21 post stem cell infusion with day of stem cell infusion counted as day 0). Post-transplant phase for this study ranged from day 22, until day 100-post stem cell infusion. Apart from data on transfusion requirement, other patient information was accessed and analyzed, which included, patient demographic details [Table 1], diagnosis and indication for HSCT [Table 2].
|Table 2: Indications for hematopoietic stem cell transplantation and type of transplant|
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For allogeneic HSCT cases, donor data were accessed to determine the degree of HLA match, relation with patient and donor blood group.
As per institutional policy, PRBC transfusions were administered for stable patients with hemoglobin of <7 g/dl. Whereas, in cases presenting with symptomatic anemia or bleeding, transfusion of PRBC was based on clinical assessment irrespective of hemoglobin levels. Prophylactic PLT transfusions were administered to nonbleeding patients at PLT counts <10,000/μl. For cases presenting with additional risk of bleeding (presence of mucositis, fever, sepsis, deranged coagulation profile), the threshold for prophylactic PLT transfusions was PLT count of <20,000/μl.
Processing of packed red blood cell and platelet units
During the initial period of study (2007–2010), 95% of HSCT patients received apheresis platelets (AP) and 5% of cases received pooled-leukofiltered random donor PLT prepared by buffy coat method from whole blood donations. After 2010, there was a change in institutional transfusion policy and all HSCT patients received only APs. All transfused PLT and PRBCs were leukodepleted and irradiated. Plasma volume reduction for APs was performed in cases where patients had ≥2 allergic reactions to plasma products, and in the event of ABO-mismatched PLT transfusions, to minimize the amount of incompatible antibodies exposure to recipient. As per institutional policy, all the PRBCs and APs transfused to HSCT patients during peri and posttransplant period were compulsorily tested for bacterial contamination using automated blood culture methods (Pall eBDS before 2016 and BacT/ALERT 2016 onward).
Descriptive statistics (mean, standard deviation, median) were used for patient's baseline demographic, disease, and transplant characteristics. Comparison of patient's characteristics used Chi-square tests for categorical variables and nonparametric test for continuous variables. The primary endpoints of the study were the number of PRBC and PLT units transfused. Distributions of the number of PRBC and PLT units transfused were highly skewed across all three phases of HSCT. Negative binomial regression model was used for assessing incidence risk ratio (IRR) which represents the ratio of subcategory value (number of units transfused) to the reference group value in each category. All tests were two-sided and performed using SPSS software (version 21.0, Armonk, NY, USA: IBM Corp.), with P ≤ 0.05 considered statistically significant.
| Results|| |
A total of 617 adult patients were included in this study with a mean age of 37.3 ± 12.7 years (range 16.5–65 years). 451 (73%) patients were males and 166 (27%) were females. Male to female ratio of the patient population was 2.7:1 [Table 1].
Overall, the most common indication for HSCT was multiple myeloma (MM) followed by acute myeloid leukemia (AML) and Hodgkin's lymphoma. The commonest indications for HSCT in autologous and allogenic group were MM and AML respectively [Table 2].
During pre-transplant period, 29.7% of the evaluable patients required either PRBC or PLT transfusions. During peri-transplant phase, 90.4% of patients required transfusion support. 61.9% and 88.8% of evaluable patients received PRBC and PLT transfusions respectively in peri-transplant phase. Number of patients with transfusion needs decreased remarkably in post-transplant phase (21.4%), with only 19.4% and 17% needing PRBC and PLT transfusion respectively. The median number of PRBC and PLT units given along with range across the 3 phases of HSCT is presented in [Table 3].
|Table 3: Number of patients receiving packed red blood cell and platelets transfusion during the pre-, peri- and post-transplant phase of hematopoietic stem cell transplantation|
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Packed red blood cell transfusion
Patients undergoing allogenic HSCT required a significantly higher (P < 0.05) number of PRBC transfusion compared to autologous HSCT across all three phases of transplant. The median number of PRBC units transfused to HSCT patients along with range is presented in [Table 4]. Among the allogenic HSCT cases, there was no significant difference in PRBC requirement among patients receiving graft from complete or haploidentical HLA-matched, related or unrelated donor [Table 4]. There was no significant difference between PRBC requirements of ABO identical and incompatible allogenic HSCT patients [Table 4].
|Table 4: Packed red blood cell utilization in different types and phases of hematopoietic stem cell transplantation|
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Subset analysis based on diagnosis with leukemia as reference group revealed that the lymphoma cases had a marginally higher PRBC requirement compared to leukemia patients in pre- and peri-transplant period. However, this was not statistically significant. The PRBC requirement in lymphoma cases was significantly lower (P < 0.05) than leukemia cases during post-transplant phase [Table 4]. Across all three phases of transplant, the requirement of PRBC was significantly less among MM patients when compared to leukemia patients [Table 4]. Subset analysis of anemia group (comprising cases of Aplastic anemia, Myelodysplastic syndrome and primary myelofibrosis) with leukemia group as reference revealed a significantly higher (P < 0.05) PRBC requirement in pre-and peri-transplant phase among anemia group patients. However, this significance was lost in post-transplant phase [Table 4], even though the requirement of PRBC continued to be higher in this group.
Allogenic HSCT cases required significantly higher (P < 0.05) number of PLT units in comparison to autologous across all three phases of transplant. The median number of units transfused along with range, IRR and P values are presented in [Table 5]. Among the allogenic HSCT cases during the peri-transplant phase, there was a significantly higher (P < 0.05) PLT requirement among patients receiving graft from haploidentical HLA-matched donor compared to those receiving graft from HLA-matched related donor [Table 5]. During peri-transplant phase, the requirement of PLT units was significantly higher (P < 0.05) in cases of Major ABO incompatible HSCT in comparison to ABO identical HSCT.
|Table 5: Platelets utilization in different types and phases of hematopoietic stem cell transplantation|
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Subset analysis with leukemia as a reference group revealed a significantly higher PLT requirement in HSCT performed for lymphoma cases (P < 0.05) when compared to HSCT performed for leukemia cases. This difference was not significant in pre and posttransplant phase. MM patients undergoing HSCT required significantly less PLT across all 3 phases of transplant when compared to patients undergoing HSCT for leukemia [Table 5]. Subset analysis of anemia group with leukemia group as reference revealed a significantly higher (P < 0.05) PLT requirement in pre-and peri-transplant phase among anemia group patients. However, this significance was lost in post-transplant phase [Table 5], even though the requirement of PLTs continued to be higher in this group.
| Discussion|| |
Being an apex HSCT center, our transfusion services often face unique challenges related to blood component inventory management as the HSCT recipients are known to have substantial and sustained transfusion requirements., This study analyzed the data of transplants performed over many years with varied diagnoses and with substantial number of subjects. Complications during peri- and post-transplant phase play a major role in transfusion requirement of HSCT patients and have a bearing on institutional transfusion policy. There are reports stating that a majority of hospitalized HSCT recipients are febrile or vulnerable to infections, and have additional risk of bleeding due to mucositis, deranged coagulation profile and similar complications related to GvHD. These risks mandate a need for a higher PLT transfusion threshold. Our institutional transfusion policy takes into consideration these risks and complications while defining the threshold levels for PRBC or PLT transfusions. It is historically reported that the transfusion considerations in HSCT patients vary across the type (e.g., autologous and allogenic, related and unrelated, etc.) and phase (pre-, peri- and post-transplantation) of HSCT. The current study tried to identify variations in transfusion requirement in our patient population across the type and phases of transplant.
Autologous and allogenic hematopoietic stem cell transplantation
In our study, more number of patients (90.4%) received PRBC and PLT transfusion during peri-transplant phase as compared to the pre-and post-transplant phase [Table 3]. Mean requirement of PRBC and PLT was significantly higher in allogenic transplant setting across all three phases of HSCT. Our findings were similar to earlier studies reporting a higher and longer transfusion support for allogenic transplant recipients due to engraftment related challenges of hematopoietic reconstitution during peri-transplant phase and complications in posttransplant period. In this study, up to 9.6% of patients (predominantly autologous HSCT) did not require any blood component transfusion in peri-transplant phase. Liesveld et al. have reported similar findings wherein an autologous source of stem cells was significantly associated with no PLT nadir, 11.6% patients did not require PLT support, and 20% did not require PRBC support and 5% had no transfusions of either PRBCs or PLT. Datta et al. have reported that around 5% of auto-HSCT cases did not require any PRBC transfusion. Studies conducted by Ballen et al. have showed that autologous stem-cell transplantation can be performed safely without the use of any blood products.,,,
HLA-matched related/unrelated and haploidentical allogeneic hematopoietic stem cell transplantation
In our study, the recipients of HLA haploidentical graft needed more number of PRBC in peri- and post-transplant phase. The PLT requirement in these cases was higher across all three phases. This difference in transfusion requirement can be attributed to delayed engraftment, higher incidence of graft rejection or GvHD in haploidentical transplants. Prolonged engraftment time leaves scope for higher chance of infections during peri-transplant period which also increases the transfusion requirement in recipients.,,
ABO identical and ABO-incompatible allogeneic hematopoietic stem cell transplantation
In this study, there was no significant difference in PRBC requirement among HSCT recipients based on ABO compatibility between patient and donor. There are various reports in literature about the impact of ABO compatibility on transfusion requirements in HSCT patients. One study from India has reported that ABO-identical did not affect transfusion requirement in HSCT patients, while some studies have reported that patients with major/bi-directional ABO-incompatibilities require more PRBC transfusions than ABO-compatible and minor ABO-mismatched graft recipients.,,,,,, Patients receiving major and bi-directionally ABO-incompatible transplants are known to require more transfusions because of delayed cellular engraftment and red cell aplasia. However, in our study, the PRBC requirement did not vary significantly with graft ABO type. Our institute follows restrictive transfusion policy and strict adherence to guidelines might have helped to minimize the transfusions in these patients. In our study, the PLT requirement in Major ABO incompatible HSCT was significantly higher in peri-transplant period only. This may be explained by the reported variable expression of group A and B substances on PLT, which might make donor PLT targets for the same isohemagglutinins that lysed donor RBC. It is possible that studies that are more specific will demonstrate other factors predictive of transfusion requirement in this setting.
Diagnosis and indications for hematopoietic stem cell transplantation
There are a few studies, which indicate that primary diagnosis of the patient may have an impact on hematopoietic recovery after HSCT, which might result in increased transfusion requirement. In this study, we identified an increased need for PLT and PRBC support for leukemia, AA, and MDS patients compared to myeloma and lymphoma group of patients. The difference could be due to earlier engraftment in myeloma and lymphoma cases in comparison to leukemia, AA, and MDS cases. Few studies have showed that the leukemia group had delayed hematopoietic recovery when compared with other diagnoses., It has been reported that PLT transfusions are higher in HSCT performed in patients with acute leukemia owing to delayed PLT recovery in comparison to other diseases., However, few studies did not find this difference.,,
We conclude that the transfusion needs of a robust HSCT program vary significantly based on the type of transplant, donor type, ABO compatibility, and primary diagnosis. Allogeneic HSCT, haploidentical donor type, primary diagnosis of leukemia, aplastic anemia, myelodysplastic syndrome, and primary myelofibrosis are the predictors for higher transfusion requirements at our center. As higher transfusion requirements may translate into increased costs of treatment, a study like this can help in managing blood component inventory and planning treatment costs of an HSCT program.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Department of Transfusion Medicine, Tata Memorial Center-Advanced Center for Treatment, Research and Education in Cancer, Homi Bhabha National Institute, Navi Mumbai - 410 210, Maharashtra
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]