Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report.

Background: Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy.

Methods: By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post-BMT. For vital status information, the medical records, the National Death Index, and the Accurint database were used.

Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect.

We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events.

Impact of Allele-Level HLA Mismatch on Outcomes in Recipients of Double Umbilical Cord Blood Transplantation.

The impact of allele-level HLA mismatch is uncertain in recipients of double umbilical cord blood (UCB) transplantation. We report a single-center retrospective study of the clinical effect of using allele-level HLA mismatch HLA-A, -B, -C, -DRB1, and -DQB1 of the 2 UCB units. We studied 342 patients with hematologic malignancy.

Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics.

Acute graft-versus-host disease (aGVHD) is associated with high risk of morbidity and mortality and is a common complication after double umbilical cord blood (UCB) transplantation. To reduce these risks, we established a method of CD4(+)CD25(+)FoxP3(+) T regulatory cell (Treg) enrichment from cryopreserved UCB followed by a 18 (+) 1-day expansion culture including anti-CD3/anti-CD28 antibody-coated beads and recombinant human interleukin-2. In a "first-in-human" clinical trial, we evaluated the safety profile of UCB Treg in 23 patients.

Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade.

Although the study of natural killer (NK) cell alloreactivity has been dominated by studies of killer cell immunoglobulin-like receptors (KIRs), we hypothesized that NKG2A and LIR-1, present on 53% +/- 13% and 36% +/- 18% of normal NK cells, respectively, play roles in the NK cell killing of primary leukemia targets. KIR(-) cells, which compose nearly half of the circulating NK cell population, exhibit tolerance to primary leukemia targets, suggesting signaling through other inhibitory receptors. Both acute myelogenous leukemia and acute lymphoblastic leukemia targets were rendered susceptible to lysis by fresh resting KIR(-) NK cells when inhibitory receptor-major histocompatibility class I interactions were blocked by pan-HLA antibodies, demonstrating that these cells are functionally competent.

Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units.

Umbilical cord blood (UCB) transplantation is potentially curative for acute leukemia. This analysis was performed to identify risk factors associated with leukemia relapse following myeloablative UCB transplantation. Acute leukemia patients (n = 177; 88 with acute lymphoblastic leukemia and 89 with acute myeloid leukemia) were treated at a single center.

Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome.

Purpose: Analysis of hematopoietic cell transplantation (HCT) for high-risk or recurrent acute lymphoblastic leukemia (ALL) using different donor sources is confounded by variable conditioning and supportive care.

Patients And Methods: We studied 623 consecutive ALL myeloablative HCT (1980 to 2005). Donors were autologous (n = 209), related (RD; n = 245), unrelated (URD; n = 100), and umbilical cord blood (UCB; n = 69).

Promising progression-free survival for patients low and intermediate grade lymphoid malignancies after nonmyeloablative umbilical cord blood transplantation.

Nonmyeloablative hematopoietic cell transplantation (HCT) has been used to treat patients with advanced or high-risk lymphoid malignancies. We studied 65 patients (median age 46 years) receiving an umbilical cord blood (UCB) graft after a single conditioning regimen consisting of cyclophosphamide (50 mg/kg) on day -6, fludarabine (40 mg/m(2)) daily on days -6 to -2, as well as a single fraction of total-body irradiation (TBI) (200 cGy) along with cyclosporine mycophenolate mofetil immunosuppression. Median time to neutrophil and platelet recovery was 7.

Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor.

The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source to suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients, and compared the treatment-related mortality (TRM) and overall survival (OS) of RIC HCT in patients older than 55 years using either MRD (n = 47) or, in patients with no 5 of 6 or 6 of 6 HLA compatible related donors, UCB (n = 43).

Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study.

We assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.

Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease.

We evaluated the efficacy of umbilical cord blood (UCB) in the setting of a nonmyeloablative regimen consisting of fludarabine (200 mg/m2), cyclophosphamide (50 mg/kg), and a single fraction of total body irradiation (200 cGy) with cyclosporine and mycophenolate mofetil for posttransplantation immunoprophylaxis. The target cell dose for the UCB graft was 3.0 x 10(7) nucleated cells/kg, resulting in the selection of a second partially human leukocyte antigen-matched UCB unit in 85%.

Good manufacturing practices production of natural killer cells for immunotherapy: a six-year single-institution experience.

Background: Natural killer (NK) cells, a subset of lymphocytes and part of the innate immune system, play a crucial role in defense against cancer and viral infection. Herein is a report on the experience of clinical-scale, good manufacturing practices (GMPs) production of NK cells to treat advanced cancer.

Study Design And Methods: Two types of NK cell enrichments were performed on nonmobilized peripheral blood mononuclear cell apheresis collections with a cell selection system (CliniMACS, Miltenyi): CD3 cell depletion to enrich for NK cells and CD3 cell depletion followed by CD56 cell selection to obtain a more pure NK cell product.

Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma.

Autologous hematopoietic stem cell transplantation (ASCT) has become standard therapy for primary refractory (PR REF) or relapsed (REL) Hodgkin's lymphoma (HL); however, more than half of these patients eventually relapse and die of their disease. We studied long-term outcomes and evaluated factors influencing progression-free survival (PFS) in 141 patients with PR REF or REL HL who underwent ASCT between 1985 and 2003. Median age at ASCT was 30 years (range, 7-60 years); 21 patients had PR REF, and 120 had REL HL.

Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.

Long-term follow-up after autologous hematopoietic stem cell transplantation for low-grade non-Hodgkin lymphoma.

Autologous hematopoietic stem cell transplantation (AHSCT) in low-grade non-Hodgkin lymphoma (NHL) can result in a prolonged remission, although most patients eventually relapse and die of their disease. We report long-term outcomes of AHSCT for patients with relapsed low-grade NHL. Between May 1983 and 2001, 67 patients with relapsed or refractory stage III and IV low-grade NHL received an AHSCT at the University of Minnesota at a median of 2.

Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.

We previously demonstrated that autologous natural killer (NK)-cell therapy after hematopoietic cell transplantation (HCT) is safe but does not provide an antitumor effect. We hypothesize that this is due to a lack of NK-cell inhibitory receptor mismatching with autologous tumor cells, which may be overcome by allogeneic NK-cell infusions. Here, we test haploidentical, related-donor NK-cell infusions in a nontransplantation setting to determine safety and in vivo NK-cell expansion.

Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy.

Limited umbilical cord blood (UCB) cell dose compromises the outcome of adult UCB transplantation. Therefore, to augment graft cell dose, we evaluated the safety of the combined transplantation of 2 partially human leukocyte antigen (HLA)-matched UCB units. Twenty-three patients with high-risk hematologic malignancy (median age, 24 years; range, 13-53 years) received 2 UCB units (median infused dose, 3.

Autologous hematopoietic cell transplantation for chronic myelogenous leukemia.

Experimental and clinical evidence for persistence of polyclonal Philadelphia chromosome negative (Ph-) progenitors in chronic myelogenous leukemia (CML) patients has provided the rationale for autologous transplantation. Clinical trials of autologous transplantation suggest that this procedure can induce cytogenetic remissions in a subset of patients and may be associated with longer-than-expected patient survival. Most autologous transplant recipients, however, continue to have evidence of persistent leukemia.

Late effects in survivors of chronic myeloid leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study.

The purpose of this study was to analyze medical late effects among patients with chronic myeloid leukemia (CML) treated with hematopoietic cell transplantation (HCT). Subjects included 248 CML survivors who received an HC transplant (related donors [RDs], n = 150; unrelated donors [URDs], n = 70; or autologous, n = 28) and had survived at least 2 years, and a comparison group of 317 siblings. Subjects completed a 238-item survey on medical late effects.

Donor chimerism does not predict response to donor lymphocyte infusion for relapsed chronic myelogenous leukemia after allogeneic hematopoietic cell transplantation.

We studied the effect of donor chimerism level on the outcome of donor lymphocyte infusion (DLI) therapy in 42 patients with persistent or relapsed hematologic malignancies after non-T cell-depleted allogeneic hematopoietic cell transplantation. Seventy-five percent of chronic myelogenous leukemia (CML) and 39% of non-CML patients entered remission after DLI therapy. Remission and survival rates were similar for CML patients irrespective of their pre-DLI donor chimerism levels; however, remission occurred sooner in patients with > or =10% pre-DLI donor chimerism.

Determinants of survival after human leucocyte antigen-matched unrelated donor bone marrow transplantation in adults.

Unrelated donor (URD) bone marrow transplantation (BMT) in adults can be associated with high non-relapse mortality (NRM). Therefore, factors determining survival in 136 human leucocyte antigen (HLA)-A, B, DRB1-matched adult BMT recipients were reviewed. Fifty-four per cent of patients had chronic myelogenous leukaemia (CML) and 36% had acute leukaemia or myelodysplasia.

The biology and treatment of chronic myelogenous leukemia.

Over the past 2 decades, our understanding of the pathobiological events underlying chronic myelogenous leukemia (CML) has grown. At the same time, effective transplant and nontransplant treatment approaches to CML have been developed that increase the options available to newly diagnosed patients, and that can cure or prolong survival in this formerly incurable disease. Newly diagnosed patients presenting with extreme leukocytosis or thrombocytosis may benefit from immediate therapy with hydroxyurea (Hydrea) and pheresis.