Bloodless Transplantation Research Articles

Letter to the editor concerning “Single-institution experience of performing bloodless transplant in Jehovah’s Witness patients” by Coltoff A, Aditya S, Solmaz A, and Steinberg A. (Hematol oncol stem cell ther 2019;12(1):44–9.)

Letter to the editor concerning “Single-institution experience of performing bloodless transplant in Jehovah’s Witness patients” by Coltoff A, Aditya S, Solmaz A, and Steinberg A. (Hematol oncol stem cell ther 2019;12(1):44–9.)

A Review of Growth Factor Support in Bloodless Autologous Hematopoietic Stem Cell Transplant.

Bloodless autologous hematopoietic cell transplantation is associated with risks of severe bleeding and profound anemia. RBC or platelet transfusions are often used to prevent these hematologic complications. However, in patients such as Jehovah's Witnesses who refuse major blood components, the lack of transfusion support is not an absolute contraindication to an autologous hematopoietic cell transplant. Pennsylvania Hospital performed the world's first bloodless hematopoietic cell transplant more than 15 years ago and has gradually improved its technique with a sizable patient population. Erythropoiesis-stimulating agents were successfully employed as part of their pretransplant regimen to prevent severe anemia. Thrombopoietin agonists' potential role in bloodless transplant is also currently being explored. Although there is limited literature, available reports in combination with physiologic reasoning may support the use of these growth factors to promote transplant success. These agents offer potential benefit and may be of utility in minimizing complications of a bloodless transplant. In this review, we summarize the available literature and offer insight into how we may incorporate growth factors to allow bloodless autologous hematopoietic cell transplantation to be an available option to patients who may otherwise be denied.

A single-institution experience of performing bloodless transplant in Jehovah's Witness patients

Objective/BackgroundAutologous stem cell transplant has been shown to prolong survival in multiple myeloma (MM). A common complication of the pre-transplant conditioning chemotherapy is severe multi-lineage cytopenias, resulting in significant transfusion requirements. Jehovah's Witnesses are members of a religious group that do not accept the transfusion of blood products. Many large transplant centers refuse to perform transplantation in Jehovah's Witnesses due to the complexity of treating cytopenic patients without blood product transfusions. However, some transplant centers that specialize in “bloodless” medicine and surgery have successfully transplanted in Jehovah’s Witnesses without transfusion support. MethodsIn order to maximize successful outcomes in this population, potential transplant candidates are treated with a variety of agents to maximize baseline hemoglobin and platelet counts. In preparation for the first two “bloodless” transplants for MM at our institution, we conducted a retrospective study of patients with MM who underwent a transplant in the preceding year. ResultsOf the 60 patients reviewed, only six required packed red blood cell transfusion, whereas 39 required at least one platelet transfusion. These findings helped us to design a novel protocol for a “bloodless” autologous transplant. We administered romiplostim, a thrombopoietin (TPO) agonist, along with aminocaproic acid, desmopressin, and vitamin K post-transplant to two Jehovah's Witness patients to mitigate the risk of thrombocytopenia. Neither patient experienced significant bleeding nor qualified for platelet transfusion, and underwent successful and uncomplicated transplantation. ConclusionWe propose that the use of romiplostim or similar TPO agonists can be used to maximize the chance of a successful “bloodless” transplant for stem cell recipients.

Safety and survival outcomes for bloodless transplantation in patients with myeloma.

High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are established components in the treatment of multiple myeloma; however, undergoing transplantation usually requires hematopoietic support, which poses a challenge among patients who are unwilling to receive blood products. Most transplant centers decline HDT/ASCT to these patients because of safety concerns. Here, the authors' institutional data on safety, engraftment parameters, and survival outcomes after bloodless ASCT (BL-ASCT) are examined among patients with myeloma. This retrospective case-control study included patients who underwent BL-ASCT and Transfusion-supported ASCT (TS-ASCT) at Emory University Hospital between August 2006 and August 2016. In total, 24 patients who underwent BL-ASCT and 70 who underwent TS-ASCT were included. The median time for neutrophil engraftment, platelet engraftment and the median length of hospital stay all were equivalent for both groups. There were no transplant-related cardiovascular complications or mortality in either the BL-ASCT group or the TS-ASCT group. The median progression-free survival was 36 months and 44 months in the BL-ASCT and TS-ASCT groups, respectively (P = .277), and the median OS was not reached in either group at a median follow-up of 59 months after ASCT (P = .627). There was no transplant-related mortality at the 100-day or 1-year mark in either group. BL-ASCT is safe and feasible; transplant-related mortality, cardiovascular and hematologic complications are similar to those associated with TS-ASCT. Furthermore, BL-ASCT can yield similar engraftment and survival parameters comparable to those observed with TS-ASCT.

178 - A Single Institution Experience of Performing Bloodless Transplant in a Jehovah's Witness Patient Based on Data Gathered from Review of Transfusion Support Requirements in Autologous Stem Cell Transplantation for the Treatment of 60 Myeloma Patients

Background: High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been shown to prolong survival in patients with multiple myeloma. A common and expected complication of pre-transplant conditioning chemotherapy is severe multi-lineage cytopenias, which results in significant transfusion requirements. Jehovah's Witnesses (JWs) are members of a large and growing religious group that do not accept transfusion of blood products, regardless of circumstance. Many large transplant centers refuse to transplant JWs due to the complexity of treating cytopenic patients without blood product transfusions. However, some transplant centers that specialize in bloodless medicine and surgery have successfully transplanted a large number of JWs without transfusion support. In order to increase the likelihood of successful outcomes in this population, potential ASCT candidates are treated with a variety of agents to maximize baseline hemoglobin and platelet counts. Methods: This is a retrospective case series of patients with multiple myeloma who underwent an ASCT at our institution in 2016. Sixty patients were included. All patients were greater than 18 years of age, and significant inclusion criteria included a high-dose melphalan conditioning regimen (200 mg/m2), a disease status of partial response or better at time of transplantation, and peripheral blood counts of hemoglobin ≥ 10 g/dL and platelet > 100 × 109/L prior to the initiation of melphalan. Results: A total of 60 cases were reviewed. Only 6 patients (10%) required at least 1 red blood cell (pRBC) transfusion while 39 patients (65%) required at least 1 platelet transfusion. The median time to first platelet transfusion was 10 days (range, 9-13 days) and the median time to first pRBC transfusion was 11 days (range, 10-13 days). We observed that majority of patients in our study required platelet transfusion whereas only 10% required pRBC transfusion. These findings assisted in designing a novel protocol for bloodless autologous transplant in JWs. We plan to give a JW patient romiplostim 4 mcg/kg weekly on day +2 post-ASCT to enhance platelet recovery and decrease risk of thrombocytopenia related bleeding, in addition to standard-of-care conservative bleeding risk reduction techniques. Additionally, we plan to judiciously use aminocaproic acid, erythropoietin, desmopressin and vitamin K in conjunction with romiplostim to keep hemoglobin stable and minimize bleeding risk. Conclusion: The majority of multiple myeloma patients with a baseline hemoglobin ≥ 10 g/dL and platelet > 100 × 109/L s only require platelet transfusion after ASCT. The frequency of severe thrombocytopenia is a limitation for JWs who would benefit from this procedure. We propose using romiplostim as an adjunct to conservative bleeding risk reduction techniques in a JW patient.

Bloodless Lung Transplantation in Jehovah's Witnesses: Impact on Perioperative Parameters and Outcome Compared With a Matched Control Group

BackgroundJehovah's Witnesses (JW) refuse to receive blood products due to their religious beliefs. Bloodless transplantation programs have made the successful transplantation of solid organs like heart, liver, kidney, and pancreas in JW feasible. In this study we present the third and fourth case of a successful bloodless lung transplantation and analyze perioperative parameters and outcome with a strictly selected matched control group (CG). MethodsTwo JW patients suffering from idiopathic pulmonary fibrosis had single lung transplantation in the transfusion-free program. Ten of 113 patients (8.8%) undergoing lung transplantation fulfilled the matching criteria and served as CG. Perioperative parameters including blood loss and transfusions were collected from the charts. Regarding outcome parameters arterial blood gas, lung function testing, length of stay, and survival were analyzed. ResultsConcerning perioperative parameters no significant differences could be found between both groups except for the creatinine level, which was significantly lower in the JW group on postoperative day 0 (P = .037), and the hemoglobin and hematocrit levels, which were significantly higher in the JW group on postoperative day 3 (P = .032 and P = .041, respectively). The analysis of the outcome parameters revealed significantly higher postoperative lung functional testing values forced expiratory volume after 1 second (FEV1) and forced vital capacity (FVC) in the JW group compared with the CG (P = .037 and P = .036, respectively). ConclusionBloodless lung transplantation is feasible in carefully selected JW recipients. Comparing JW to CG, no statistically significant difference in the perioperative course and a trend towards a favorable postoperative lung function outcome were detected.

SCT in Jehovah's Witnesses: the bloodless transplant

Auto-SCT and Allo-SCT are procedures conventionally associated with intensive transfusion support. This dependence has historically prevented SCT in individuals with religious or personal objections to transfusion. More recently, a growing body of literature supports the feasibility of 'bloodless transplants': SCT without the transfusion of RBCs, plts or plasma. It is possible to perform 'bloodless' autologous or reduced-intensity allogeneic transplants in properly selected patients. The success of these procedures depends on the transplantation technique and on meticulous attention to blood conservation and supportive care. In this study, the literature supporting bloodless transplantation will be reviewed. Supportive measures such as the optimal stimulation of erythropoiesis and thrombopoiesis in the transplant patient will be discussed, as will the prevention and management of bleeding during extreme thrombocytopenia. Many of these techniques, learned and refined in Jehovah's Witnesses, may help reduce bleeding and transfusion requirements in the general transplant population.