Yen-Michael S. Hsu

Autologous Stem Cell Mobilization and Collection.

Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects.

Cord blood chimerism and relapse after haplo-cord transplantation

Abstract Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18–72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p < 0.0001) and decrease in one year progression-free (20% versus 55%, p = 0.004) and overall survival (30% versus 62%, p = 0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p = 0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p = 0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.

Haplo-cord transplant: HLA-matching determines graft dominance

Haplo-cord transplantation combines the infusion of CD34 selected third party cells from a haplo-identical donor, with an umbilical cord blood (UCB) graft from an unrelated donor.[1–5] In a majority of the cases, initial engraftment from the haplo-identical donor is superseded by dominance of the UCB graft. But in some cases, only the haplo-graft persists. In previous studies, we found that patients who received very high CD34 doses from the haplo-identical donor had impaired/delayed UCB engraftment.[6] More recently, we have limited the cell dose of the haplo-graft to 3–5 10 CD34/kgrec. But occasional cases of haplo-dominance continue to occur. Here we attempted to determine the additional graft and conditioning characteristics that influence the interaction between haplo-graft and cord blood graft and the eventual long-term dominance of one graft over the other. All the patients were enrolled in a prospective study of reduced intensity conditioning and haplo-cord transplantation. The study was approved by the Institutional Review Board of Weill Cornell Medical College and all patients and donors provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and registered on clinical trials.gov (NCT01810588). Cord blood units (CBUs) were selected based on human leukocyte antigen (HLA) typing and cell count. As of mid-2012, we utilized high-resolution HLA typing for HLA-A, B, C, and DR for cord graft selection.[7] In contrast with common practice, we prioritized matching over cell dose and established a minimum cell count of 1.2 10 nucleated cells/kg of the recipient’s body. After collection and prior to cryopreservation, haploidentical grafts were T-cell depleted using the Miltenyi CliniMACS device under an Investigational New Device (IND) permit from the United States Food and Drug Agency. The infused cell dose of the haplo-graft was fixed at a minimum of 3 10 CD34 cells/kg and a maximum of 5 10 CD34 cells/kg of recipient weight. Patients received fludarabine 30mg/m/d iv for 5 consecutive days (days 7, 6, 5, 4, 3), rabbit antithymocyte globulin (thymoglobulin, r-ATG) at 1.5mg/kg every other day for 3 or 4 doses, and melphalan 140mg/m/d for 1 dose on day 2.[8] Thirteen patients were also given a 400 cGray, usually because of concern over disease recurrence. One patient received TBI 600 cGray. The haplo-identical cells were infused on day 0 followed by cord blood later the same day or on day 1. Posttransplant GVHD prophylaxis consisted of tacrolimus on day 2 until day 180 and mycophenolate mofetil 1 g per oral (po) three times a day (TID) until day 28. CD3 and CD33 chimerism was studied as previously described.[9] Univariate regression models were used to analyze the relation between continuous variables and chimerism. T-tests or ANOVA were used for categorical variables. All p values are two-sided. Factors examined include (1) degree of CBU HLA-match to recipient dichotomized as 4-5-6 out of 8 HLA match vs. 7 or 8 out of 8 HLA match, (2) UCB graft CD34/kgrec collected, (3) UCB TNC/kgrec infused, (4) presence of donor-specific antibodies (DSA) against UCB graft, (5) UCB viability at the time of infusion – as defined by >90% Trypan blue exclusion vs. <90%, (6) degree of haplo-graft HLA-match to recipient HLA-dichotomized as 4–5 out of 8 HLA match vs. 6–7 out of 8 HLA match, (7) presence of DSA against haplograft, (8) use of TBI in conditioning, (9) CIBMTR Disease Risk index, (10) degree of HLA match between CBU and recipient, (11) degree of HLA match between haplo-graft and recipient, and (12) degree of HLA match between CBU graft and haplo-graft. Eighty-three patients with hematologic malignancies were enrolled between January 2012 and February 2015. Four died prior to engraftment including one due to infection, one from multi-organ failure, and two from VOD/SOS. Of the remaining 79 patients, three (4%) had complete graft failure with autologous reconstitution. Seventeen additional patients were excluded from the

Massive transfusion protocols: current best practice

Massive transfusion protocols (MTPs) are established to provide rapid blood replacement in a setting of severe hemorrhage. Early optimal blood transfusion is essential to sustain organ perfusion and oxygenation. There are many variables to consider when establishing an MTP, and studies have prospectively evaluated different scenarios and patient populations to establish the best practices to attain improved patient outcomes. The establishment and utilization of an optimal MTP is challenging given the ever-changing patient status during resuscitation efforts. Much of the MTP literature comes from the trauma population, due to the fact that massive hemorrhage is the leading cause of preventable trauma-related death. As we come to further understand the positive and negative clinical impacts of transfusion-related factors, massive transfusion practice can be further refined. This article will first discuss specific MTPs targeting different patient populations and current relevant international guidelines. Then, we will examine a wide selection of therapeutic products to support MTPs, including newly available products and the most suitable of the traditional products. Lastly, we will discuss the best design for an MTP, including ratio-based MTPs and MTPs based on the use of point-of- care coagulation diagnostic tools.

Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies

TO THE EDITOR: Drug-induced immune thrombocytopenia (DITP) is caused by drug-dependent platelet-reactive antibodies DDAbs) that induce platelet destruction when a drug is taken for which the antibody is specific.[1][1][⇓][2][⇓][3][⇓][4]-[5][5] The widely used cancer drug oxaliplatin is a

Validating and implementing the use of an infusion pump for the administration of thawed hematopoietic progenitor cells-a single-institution experience: VALIDATION OF INFUSION PUMP FOR PBSCs

Direct thaw and administration of previously cryopreserved peripheral blood stem cell products is a commonly used practice and should be performed rapidly to reduce cellular damage caused by dimethyl sulfoxide exposure. Cells are typically thawed at the bedside and infused by gravity through a high‐flow‐rate central venous catheter. An existing nontunneled catheter is occasionally used instead and often results in a slower infusion rate. To ensure expedient and consistent infusions, we validated and implemented the use of an infusion pump for thawed peripheral blood stem cells.

Logistical and safety implications of temperature-based acceptance of returned red blood cell units: TEMPERATURE-BASED ACCEPTANCE OF RBCs

AABB requires that red blood cells (RBCs) are maintained at 1 to 10°C during transport. Historically, blood banks used the 30‐minute rule for returned RBCs transported outside of validated containers. The implications of this policy have not been previously reported in a real‐life hospital setting.