A prospective study of posttransplant cyclophosphamide for unrelated donor peripheral blood stem cell transplant with special attention to graft content and the impact of a higher γδ T cell dose.

Posttransplant cyclophosphamide (PtCy) has been shown to decrease post-hematopoietic stem cell transplant acute and chronic graft-versus-host disease (GVHD). In this study, PtCy was used in 44 patients along with mycophenolate and tacrolimus with HLA matched (29) and mismatched (15) unrelated donors to determine the impact of graft content on outcome; thus, all patients had flow cytometric analysis of their graft content including the number of B cells, NK cells, and various T cell subsets. Higher γδ T cell dose was associated with the development of acute GVHD (p = .

A Phase I Trial of Sirolimus with "7&3" Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment.

Cell Therapy Informatics: Updates on the Integration of HCT/IEC Functionalities into an Electronic Medical Record System in the US to Promote Efficiency, Patient Safety, Research, and Data Interoperability.

The use of electronic health/medical record (EMR) systems has streamlined medical practice and improved efficiency of clinical care in recent years. However, EMR systems are not generally well designed to support research and tracking of longitudinal outcomes across populations, which are particularly important in hematopoietic stem cell transplantation (HCT) and immune effector cell therapy (IEC), where data reporting to registries and regulatory agencies are often required. Since its formation in 2014, the HCT EMR user group has worked with a large EMR vendor (Epic) to develop many functionalities within the EMR to improve the care of HCT/IEC patients and facilitate the capture of HCT/IEC data in an easily interoperable format.

A Prospective, Randomized Trial Examining the Use of G-CSF Versus No G-CSF in Patients Post-Autologous Transplantation.

Contemporary, prospective data regarding the impact of granulocyte-colony stimulating factor (G-CSF) on outcomes after autologous hematopoietic stem cell transplantation (Auto-HSCT) in an era when stem cell grafts are more qualitatively robust are limited. Recent retrospective analyses have not supported a beneficial effect of post-transplantation G-CSF use on major outcomes after Auto-HSCT leading to strategies to delay or eliminate the use of G-CSF altogether in this context. To test the hypothesis that the infusion of consistently higher doses of stem cells (defined as ≥4 × 10/kg) in Auto-HSCT will obviate the need for post-transplantation G-CSF.

Outcomes of two-step haploidentical allogeneic stem cell transplantation in elderly patients with hematologic malignancies.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the best curative option for the majority of patients with hematologic malignancies (HM); however, many elderly patients are excluded from transplant and outcome data in this population is still limited. The novel two-step graft engineering approach has been the main platform for allo-SCT at Thomas Jefferson University since 2006. Following administration of the preparative regimen, we infuse donor lymphocytes, followed by cyclophosphamide to induce bidirectional tolerance, then infusion of CD34-selected cells.

Case Report: Concomitant Diagnosis of Plasma Cell Leukemia in Patient With JAK2 Positive Myeloproliferative Neoplasm.

Plasma cell dyscrasias and myeloproliferative neoplasms (MPN) are hematologic malignancies arising from two distinct hematopoietic cell lineages. They rarely occur concomitantly. Here, we report a case of a patient with a recent diagnosis of a JAK2 V617F positive MPN who presented with a new diagnosis of plasma cell leukemia.

Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes.

The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization.

Autologous Stem Cell Transplantation for Multiple Myeloma: Growth Factor Matters.

Engraftment syndrome (ES) is a known complication of autologous hematopoietic stem cell transplant during neutrophil recovery. There is a limited amount of data available comparing the incidence of ES with post-transplant granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor (GM-CSF), specifically in patients with multiple myeloma. Our retrospective review of 156 patients at a single center showed that GM-CSF was associated with a higher incidence of ES compared with G-CSF (32% versus 8% of patients, P < .

Donor Lymphocyte Infusion in Hematologic Malignancies--Good to be Fresh?

Background: Donor lymphocyte infusion (DLI) has been used with variable success in a variety of hematologic malignancies.

Patients And Methods: We conducted a retrospective analysis of all patients who were treated with DLI for persistent or relapsed disease at the Temple University Bone Marrow Transplant Unit from July 1, 1993 to December 31, 2013 to evaluate the effect of the type of DLI (fresh vs. cryopreserved) on event-free survival (EFS) and overall survival (OS).

Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies.

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.

Center for International Blood and Marrow Transplant Research chronic graft-versus-host disease risk score predicts mortality in an independent validation cohort.

We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10).

Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome.

Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia.

Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active.

Older patients with myeloma derive similar benefit from autologous transplantation.

Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people ≤70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946).

Electronic medical records and quality of cancer care.

The implementation of electronic medical records (EMR) systems was mandated by the U.S. federal government in large part due to research indicating that difficulty accessing clinical data was one of the most common causes of preventable deaths.

Providing personalized prognostic information for adult leukemia survivors.

Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least 1 year after allogeneic hematopoietic cell transplantation is difficult. We analyzed 3339 patients with acute myeloid leukemia and 1434 patients with acute lymphoblastic leukemia who received myeloablative conditioning and related or unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS in 1-year survivors were no longer significant after 2 or more years.

HLA DR15 antigen status does not impact graft-versus-host disease or survival in HLA-matched sibling transplantation for hematologic malignancies.

The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007.

Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.

We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006.

Spontaneous graft versus host disease occurring in a patient with multiple myeloma after autologous stem cell transplant.

Graft versus host disease (GVHD) is a common complication of allogeneic transplant. Acute GVHD primarily affects the skin, liver, and GI tract generally within the first 100 days after transplant. GVHD following an allogeneic transplant occurs as a result of donor T-cell recognition of host alloantigens.

Risk factors associated with increased nonrelapse mortality and with poor overall survival in children with chronic graft-versus-host disease.

There is a paucity of information regarding the factors that affect nonrelapse mortality (NRM) and overall survival among children that develop chronic graft-versus-host disease (cGVHD). We performed multivariate analyses using data from the Center for International Blood and Marrow Transplant Research to identify risk factors for NRM and survival in 1117 pediatric subjects with leukemia or myelodysplastic syndrome, transplanted from related donors, unrelated donors (URD), or unrelated cord blood between 1995 and 2004. We identified 4 variables associated with higher NRM: HLA partially matched or mismatched URD, peripheral blood cell graft, Karnofsky/Lansky score < 80 at cGVHD diagnosis, and platelets < 100 × 10(9)/L at cGVHD diagnosis.

Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study.

Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004.

Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis.

Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count.

Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis.

We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA)-matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (≥ 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%).

The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission.

We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .