History of Pure Red Cell Aplasia, Essay Example

Those with hematologic deficiencies may require treatment in the form of allogenic hematopoietic peripheral blood progenitor cell transplantation (PBCPT), thereby creating an environment in which there is a lower level of invasiveness and improved recovery rates (Erker et.al 1382). ABO mismatches may be categorized into three different types: major, minor, and bidirectional, and when major mismatch occurs, there is a significant risk of destroying donor red blood cells in conjunction with antibodies to fight against erythroid antigens (Erker et.al 1383). The phenomenon known as pure red cell aplasia (PRCA) is likely in approximately 29 percent of major mismatches (Erker et.al 1383). It is suggested that PRCA may be prevented through the reduction of incompatible isohaemagglutinin titres at the pre-transplant stage; however, this has not proven to be the case and is inconsequential to the formation of PRCA in this patient population (Damodar et.al 233).

ABO blood group incompatibility may occur in patients who undergo hematopoietic progenitor cell transplantation (HCT) without sufficient blood type matching; therefore, complications such as delayed RBC engraftment, red blood cell aplasia, and other delayed hemolytic reactions (Booth et.al 1152). Furthermore, survival statistics are inconsistent, particularly as ABO-incompatible HCT may contribute to graft-versus-host disease and platelet and granulocyte engraftment (Booth et.al 1152). When ABO incompatibility is evident with donors and recipients, there is a significant risk of graft rejection and subsequent mortality through red blood cell hemolysis, red cell engraftment at a delayed rate, and pure red cell aplasia (Booth et.al 1152). Transplantation may contribute to a hemolytic reaction due to challenges in cell processing and the nature of the graft (Booth et.al 1153). In order to address PRCA effectively, immunosuppression is often employed, along with plasma exchange, donor lymphocyte infusions, and rituximab, among other options (Booth et.al 1153).

ABO mismatching has a significant impact on overall survival, according to a meta-analysis conducted by Kanda et.al (624). The nature of mismatched ABO prior to transplantation is complex in nature, depending on its severity, classified as major, minor, and bidirectional; therefore, additional studies must be evaluated in order to determine if there are any patterns of consistency within this framework, including the types of population groups that will be studied, as well as other factors that may be contradictory in determining the true impact of ABO mismatching (Kanda et.al 624). However, upon observation of the selected studies, ABO mismatching and its relationship to overall survival was not significant in related stem cell transplants, but unrelated SCTs were impacted by bidirectional and marginal mismatches (Kanda et.al 630). Nonetheless, these types of mismatches and the nature of survival under these events is not well understood and requires further investigation (Kanda et.al 631).

In a study conducted by Aung et.al (798), it was determined that 7.5 percent of patients undergoing HSCT experienced PRCA, a relatively low rate under which the termination of immunosuppression or spontaneous modification were able to resolve these deficits (Aung et.al 798). In this study, 161 patients with major mismatched donors were identified, of which this percentage was identified as having PRCA (Aung et.al 802). In addition, PRCA resolved in a spontaneous manner in seven patients in the range of 47-268 days, while five patients experienced resolution after Tacrolimus 60-100 days later (Aung et.al 802). It should also be noted that PRCA rates may vary widely from one study to the next, depending on external conditions and other factors that play a role in this process (Aung et.al 803). Therefore, additional studies are required in order to determine the true nature of these circumstances and how to best approach patients so that their survival rates are increased and improved over time.

A study conducted by Wang et.al (101) evaluated recipients of HCT provided with myeloablative or nonmyeloablative conditioning and sought to determine transfusion requirements. It was determined that those receiving myeloablative conditioning required additional transfusions of red blood cells and platelets; furthermore, it was determined that recipients categorized as ABO mismatches required a higher level of red blood cell transfusions than those who were ABO matches (Wang et.al 101). However, graft rejection/failure rates, those with acute and chronic graft-versus-host disease, relapse at two years, survival at three years, and non-relapse mortality rates were similar in patients with ABO matches, minor mismatches, and major or bidirectionally mismatched patients (Wang et.al 101). In general, nonmyeloablative recipients did not require as many red blood cell and platelet transfusions as myeloablative recipients (Wang et.al 101).

In a retrospective analysis of 1,108 patients who had allogenic hematopoietic stem cell transplantation who were also given reduced intensity conditioning (RIC HSCT), it should be noted that 40 percent of patients (n=442) were in remission when transplantation occurred, while 79 percent of patients (n=878) were given peripheral blood stem cells, 42 percent of patients (n=465) received fludarabine and busulfan along with rabbit anti-thymocyte globulins, and 255 patients received low-dose total body irradiation and fludarabine (Michallet et.al 535). For patients who were not in complete remission, there was a significant impact on overall survival and event-free survival for patients prior to transplantation events (Michallet et.al 535). Furthermore, the study indicates that there is a significant difference between overall survival and event-free survival in patients with cGVHD versus patients without cGVHD, related to the myeloablative environment (Michallet et.al 542).

In an article by Igarashi et.al (1356), 189 patients were evaluated for anti-host isohemagglutinin (IH) production and its relationship to the development of acute graft-versus-host-disease (GVHD). In those patients who exhibited IH production (19 percent or 36 patients), 10 patients presented with acute GVHD when IH was detected prior, 8 patients exhibited GVHD at the same time as IH, and 17 patients presented with GVHD when IH was detected after diagnosis (Igarashi et.al 1356). It was also determined that 45 percent of patients with ABO mismatching presented with grade II-IV acute GVHD in comparison to other patient populations (Igarashi et.al 1356). However, the study did not demonstrate that there was a significant difference between the level of IH and the level of acute GVHD that was observed (Igarshi et.al 1358). It is also known that donor T cells may have a significant impact on the development of acute GVHD, but that donor B cells remain a complex set of circumstances to evaluate (Igarshi et.al 1359).

In a study by Ludajic et.al (1400), a study involving 3,103 patients identified bidirectional ABO mismatching with severe aGVHD at stages III-V, but did not correlate with stages II-IV or general aGVHD status. It should be noted that in spite of an increase in aGVHD in this population, there was not an increase in cGVHD, TRM, or even Rh matching status or OS, thereby noting that the presence of ABO antigens does not have a significant impact on alleviating the impact of GVL (Ludajic et.al 1405). Nonetheless, it has been determined that minor ABO-mismatching has a significant impact on the development of aGVHD in patients who have received HSCT (Ludajic et.al 1405).

A study by Resnick et.al (409) examined the relationship between ABO incompatibility and myeloid engraftment, the prevalence of acute and chronic GVHD, mortality associated with GVHD, relapse, overall survival, and non-relapse mortality rates. Some of the key variables considered included disease, disease risk, age, and characteristics of donors, using a study population of 221 patients. The study determined that non-relapse mortality rates were higher in patients who were classified as having minor and major ABO incompatibility, and there was a general increase in mortality as a result of GVHD for this population group overall (Resnick et.al 409). In patients with major ABO incompatibility, there was also a general decrease in overall survival rates after one year (Resnick et.al 409). As a result, ABO incompatibility is associated with a general negative impact on the observed outcomes related to transplantation events (Resnick et.al 409).

The aforementioned studies offer a number of different perspectives regarding hematopoietic stem cell transplantation and the factors that contribute to this condition and its overall impact on patient survival rates and outcomes. These studies offer a variation of different approaches in order to determine patient responses and survival rates as related to transplantation events. It is important to note that the higher the rate of incompatibility, the higher the risk of developing graft-versus-host-disease and other complications that impact overall survival rates and mortality. Therefore, it is necessary to evaluate these conditions and to examine each patient individually in order to determine his or her potential level of risk as well as survival in the wake of these events. Recognizing the risks in advance of these events is likely to have an impact on potential outcomes for some patients and in providing a framework for future studies to evaluate this area.

Works Cited

Aung, Fleur M., et al. “Incidence and natural history of pure red cell aplasia in major ABO?mismatched haematopoietic cell transplantation.” British journal of haematology 160.6 (2013): 798-805.

Booth, Garrett S., Eric A. Gehrie, Charles D. Bolan, & Bipin N. Savani. “Clinical guide to ABO-  incompatible allogenic stem cell transplantation.” Biology of Blood and Marrow Transplantation, 19(2013): 1152-1158.

Damodar, S., B. George, J. Mammen, V. Mathews, A. Srivastava, & M. Chandy. “Pre-transplant reduction of isohaemagglutinin titres by donor group plasma infusion does not reduce the incidence of pure red cell aplasia in major ABO-mismatched transplants.” Bone Marrow Transplantation, 36, 233-235.

Erker, Christian G., Martin B. Steins, Rudolf-Josef Fischer, Joachim Kienast, Wolfgang E. Berdel, Walter Sibrowski, & Uwe Cassens. “The influence of blood group differences in allogenic hematopoietic peripheral blood progenitor cell transplantation.” Transfusion 45(2005): 1382-1390.

Igarashi, A., et al. “Anti-host isohemagglutinin production is associated with a higher risk of acute GVHD in ABO-incompatible transplantation.” Bone marrow transplantation 47.10 (2012): 1356-1360.

Kanda, Junya, Tatsuo Ichinohe, Keitaro Matsuo, Richard J. Benjamin, Thomas R. Klumpp, Primoz Rozman, Neil Blumberg, Jayesh Mehta, Sang-Kyun Sohn, and Takashi Uchiyama. ”Impact of ABO mismatching on the outcomes of allogenic related and unrelated blood and marrow stem cell transplantations for hematologic malignancies: IPD-based meta-analysis of cohort studies.” Transfusion 49(2009): 624-635.

Ludajic, Katarina, et al. “Minor ABO-mismatches are risk factors for acute graft-versus-host disease in hematopoietic stem cell transplant patients.” Biology of blood and marrow transplantation 15.11 (2009): 1400-1406.

Michallet, Mauricette, et al. “Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie

Cellulaire.” Experimental hematology 36.5 (2008): 535-544.

Resnick, Igor B., et al. “ABO incompatibility is associated with increased non-relapse and GVHD related mortality in patients with malignancies treated with a reduced intensity regimen: a single center experience of 221 patients.” Biology of Blood and Marrow Transplantation 14.4 (2008): 409-417.

Wang, Zejing, et al. “The impact of donor type and ABO incompatibility on transfusion requirements after nonmyeloablative haematopoietic cell transplantation.” British journal of haematology 149.1 (2010): 101-110.