Peripheral Blood Stem Cells versus Bone Marrow for T Cell–Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Hodgkin Lymphoma

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P = .405) and platelet (26 versus 26.5 days, P = .994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P = .761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR], .29; P = .006), PFS (HR, .38; P = .001), and GRFS (HR, .44; P = .020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant–specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor.     

Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating Factor–Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and Outcome for T Cell–Replete Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study

We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell–replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10?×?10⁶/kg CD34⁺ hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF?+?Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34⁺ HSCs on day 4 in the G-CSF?+?Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P?=?.0001), PB CD34⁺ HSC count (median 136 versus 139 cells/µL) on day 5 as well as that in the graft (2.7 versus 2.3?×?10⁶/mL, P?=?.1) were comparable between the 2 groups. The total nucleated cell count was higher (3.4 versus 3.1?×?10⁸/mL, P?=?.05), but CD4⁺ T cells (2.3 versus 2.7?×?10⁷/mL, P?=?.09) were lower in the G-CSF group with mobilization of regulatory T cells being similar. NK cells were skewed toward the CD56⁺/16^? subset in both groups, varying significantly from the steady-state NK subset ratio in PB. The time to engraftment, incidences of acute and chronic graft-versus-host disease, nonrelapse mortality, and overall survival were also similar. Addition of single-dose Px to G-CSF mobilization improves CD34 recovery and does not significantly alter the T and NK cell composition of the graft, including regulatory T cells, with no adverse impact on transplant outcomes.     

Donor Selection in T Cell–Replete Haploidentical Hematopoietic Stem Cell Transplantation: Knowns,Unknowns, and Controversies

Multiple donors are generally available for haploidentical hematopoietic stem cell transplantation. Here we discuss the factors that should be considered when selecting donors for this type of transplantation according to the currently available evidence. Donor-specific anti-HLA antibodies (DSAs) increase the risk of graft failure and should be avoided whenever possible. Strategies to manage recipients with DSAs are discussed. One should choose a full haplotype mismatch rather than a better-matched donor and maximize the dose of infused hematopoietic cells. Donor age and sex are other important factors. Other factors, including predicted natural killer cell alloreactivity and consideration of noninherited maternal alleles, are more controversial. Larger studies are needed to further clarify the role of these factors for donor selection in haploidentical hematopoietic stem cell transplantation.     

Normalization of the Peripheral Blood T Cell Receptor Vβ Repertoire After Cultured Postnatal Human Thymic Transplantation in DiGeorge Syndrome

Complete DiGeorge syndrome is an immunodeficiency disease characterized by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transplantation, flow cytometry, T cell receptor V sequence analysis, and cell function studies showed the presence of oligoclonal populations of nonfunctional clonally expanded peripheral T cells that were derived from pretransplantation T cells present in the skin. However, at 3 months posttransplantation, a biopsy of the transplanted thymus showed normal intrathymic T cell maturation of host T cells with normal TCR V expression on thymocytes. By 9 months posttransplantation, peripheral T cell function was restored and the TCR V repertoire became polyclonal, coincident with the appearance of normal T cell function. These data suggest that the transplanted thymus was responsible for the establishment of a new T cell repertoire via thymopoiesis in the chimeric thymic graft.     

T Cell–Depleted Related HLA-Mismatched Peripheral Blood Stem Cell Transplantation as Salvage Therapy for Graft Failure after Single Unit Unrelated Donor Umbilical Cord Blood Transplantation

Graft failure is a severe treatment complication of unrelated donor umbilical cord blood transplantation (UCBT). Its incidence seems to be higher after UCBT than after transplantation with bone marrow or peripheral blood stem cells (PBSCs). The only curative option is to perform a second transplantation; however, both the ideal stem cell source and the conditioning regimen for this salvage transplantation remain unclear. We report a series of 11 patients who underwent haploidentical PBSC transplantation (PBSCT) as salvage therapy for graft failure after a previous UCBT. The reduced-intensity conditioning regimen consisted of fludarabine 150 mg/m² for 3 days and horse antithymocyte globulin 8 mg/kg for 4 days. Ex vivo CD34⁺ positive selection was performed in all cases, and no post-transplantation graft-versus-host disease prophylaxis was used. Six of the 9 evaluable patients (67%) eventually engrafted, at a median time of 10 days. The cumulative incidence of engraftment at 28 days was 64% (95% confidence interval [CI], 35% to 92%). Two patients relapsed after PBSCT. The cumulative incidence of TRM was 55% at 2 years (95% CI, 25% to 84%), and the probability of overall survival at 2 years was 36%. Our findings suggest that haploidentical ex vivo T cell–depleted PBSCT is a feasible alternative for treating graft failure after UCBT.     

Unexpected High Incidence of Human Herpesvirus-6 Encephalitis after Naive T Cell–Depleted Graft of Haploidentical Stem Cell Transplantation in Pediatric Patients

The CD45RA T cell depletion (TCD) method has been used to deplete naive T cells, preventing graft-versus-host disease (GVHD) but preserving memory cells, providing immediate functional T cells with anti-infection, antileukemia, and antirejection effects. We describe a series of 25 consecutive high-risk patients with leukemia who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with CD45RA TCD. Each patient received 2 cell products: 1 created by CD34 positive selection and the other through CD45RA depletion from the CD34 negative fraction by a CliniMACS device. CD45RA-depleted haplo-HSCT was well tolerated, with rapid engraftment and low risk of severe acute GVHD and chronic GVHD. Although this treatment achieved a good control of viral reactivations, such as cytomegalovirus and adenovirus, we observed an unexpectedly high rate of limbic encephalitis due to human herpesvirus-6 (HHV-6; 8 cases). Characteristically, the infection appeared early in almost all patients, just after the engraftment. Although no patient died from encephalitis, 1 patient showed neuropsychological sequelae, and another experienced secondary graft failure just after the HHV-6 reactivation.     

Thiotepa,Fludarabine, and Busulfan Conditioning Regimen before T Cell–Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.     

Immunologic Recovery in Children after Alternative Donor Allogeneic Transplantation for Hematologic Malignancies: Comparison of Recipients of Partially T Cell–Depleted Peripheral Blood Stem Cells and Umbilical Cord Blood

Impaired immunologic recovery (IR) after hematopoietic stem cell transplantation (HSCT) is associated with increased risk for infections and relapse. Stem cell source and graft manipulation influence the kinetics of IR. Partial T cell depletion of peripheral blood stem cell (PBSC) grafts is a novel alternative method of graft manipulation for children. We compared IR in children undergoing HSCT for hematologic malignancies receiving either T cell–depleted (TCD)-PBSCs (n = 55) or umbilical cord blood (UCB) (n = 21) over a 7-year period at a single institution. PBSC grafts underwent ex vivo negative selection for CD3⁺ cells using the CliniMACS system with partial T cell add-back. Recovery of CD4⁺ T cells was significantly delayed in TCD-PBSC recipients compared with UCB recipients, owing to impaired CD4⁺/CD45RA⁺ (naïve) T cell lymphopoiesis. Recovery of total CD3⁺ cells and CD3⁺/CD8⁺ cells was similar in the 2 groups. The TCD-PBSC recipients had a marked deficit in CD19⁺ and, to a lesser extent, IgA/IgM, owing to the need for B cell depletion of these grafts to attenuate the risk of lymphoproliferative disease after TCD HSCT. There were no significant between-group differences in response to mitogen stimulation, time to independence from intravenous immunoglobulin supplementation, or incidence of viral reactivation. Transplantation outcomes of relapse, transplantation-related mortality, event-free survival, and overall survival were similar in the 2 groups. Efforts to enhance IR after partial TCD-PBSC transplantation, such as selective αβ T cell depletion, hold promise for further improvement of this transplantation approach.     

Total Body Irradiation and Cyclophosphamide Plus Antithymocyte Globulin Regimen Is Well Tolerated and Promotes Stable Engraftment as a Preparative Regimen before T Cell–Replete Haploidentical Transplantation for Acute Leukemia

We compared total body irradiation (TBI, 700 cGy)/cyclophosphamide (Cy, 3.6 g/m²)/simustine (250 mg/m²) plus antithymocyte globulin (ATG) (TBI/Cy plus ATG) with cytarabine (8 g/m²)/i.v. busulfan (Bu, 9.6 mg/kg)/Cy (3.6 g/m²)/simustine (250 mg/m²) plus ATG (modified Bu/Cy plus ATG) as preparative therapy in T cell–replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive patients using TBI/Cy plus ATG regimen for T cell–replete haplo-HSCT (TBI group) at our center were eligible, which contained 28 high-risk and 10 standard-risk patients. A nested case-control study was designed. Seventy-seven patients using modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1 to 3:1 ratio matching for age, disease and status, year of HSCT (±2 years), and length of follow-up. Only 1 graft failure occurred in the TBI group. The incidence and time of neutrophil and platelet engraftment were comparable between the 2 groups. Severe grades III/IV graft-versus-host disease was observed in 13.4% of Bu group and only 2.6% of TBI group (P = .083). More toxicity of the liver (37.7% versus 10.5%; P = .002) and more hemorrhagic cystitis occurred in the Bu group (49.3% versus 23.7%, P = .008). Diarrhea was more common in the TBI group (44.7% versus 22.1%; P = .031). No significant differences were found in the 2-year incidences of relapse (26.5% for TBI group versus 32.3% for Bu group, P = .742), 1-year transplant-related mortality (12.6% versus 16.2%, P = .862), 2-year overall survival (60.2% versus 57.0%, P = .937), and 2-year incidence of disease-free survival (57.9% versus 56.6%, P = .845) between the 2 groups. We conclude that the TBI/Cy plus ATG regimen seems to be feasible in T cell–replete haplo-HSCT, which promotes stable engraftment and a lower incidence of liver toxicity and hemorrhagic cystitis. However, longer follow-up is necessary to determine the late relapse rate and late toxicity.     

Engineering Human Peripheral Blood Stem Cell Grafts that Are Depleted of Naïve T Cells and Retain Functional Pathogen-Specific Memory T Cells

Graft-versus-host disease (GVHD) is a frequent major complication of allogeneic hematopoietic cell transplantation (HCT). Approaches that selectively deplete T cells that cause GVHD from allogeneic stem cell grafts and preserve T cells specific for pathogens may improve HCT outcomes. It has been hypothesized that the majority of T cells that can cause GVHD reside within the naïve T cell (T_N) subset, and previous studies performed in mouse models and with human cells in vitro support this hypothesis. As a prelude to translating these findings to the clinic, we developed and evaluated a novel 2-step clinically compliant procedure for manipulating peripheral blood stem cells (PBSC) to remove T_N, preserve CD34⁺ hematopoietic stem cells, and provide for a fixed dose of memory T cells (T_M) that includes T cells with specificity for common opportunistic pathogens encountered after HCT. Our studies demonstrate effective and reproducible performance of the immunomagnetic cell selection procedure for depleting T_N. Moreover, after cell processing, the CD45RA-depleted PBSC products are enriched for CD4⁺ and CD8⁺ T_M with a central memory phenotype and contain T_M cells that are capable of proliferating and producing effector cytokines in response to opportunistic pathogens.     

Higher CD45RA+ Regulatory T Cells in the Graft Improves Outcome in Younger Patients Undergoing T Cell–Replete Haploidentical Transplantation: Where Donor Age Matters

To understand the phenomenon of early alloreactivity (EA) in younger children undergoing post-transplantation cyclophosphamide (PTCy)-based haploidentical transplantation, we studied the graft composition and the immune reconstitution in 32 consecutive patients (aged 2 to 25 years) undergoing PTCy and T cell costimulation blockade based peripheral blood stem cell transplantation with emphasis on CD45RA⁺ subset of regulatory T cells (Tregs). All but 1 engrafted, and 14 patients experienced EA (acute graft-versus-host disease grades II to IV, n?=?8; and post-transplantation hemophagocytic syndrome, n?=?6) with a cumulative incidence of 43.7%; 42% developed mild chronic graft-versus-host disease. The overall survival was 70.2% with a nonrelapse mortality of 16.8% at a median of 19 months. Age < 10 years, donor age > 45 years, and poor recovery of Tregs correlated with EA. Not Tregs but higher CD45RA⁺ Tregs in the graft was associated with less EA (11.7% versus 32.5%, P = .0001). Higher donor age correlated with a lower CD45RA⁺ Tregs in the graft (P = .01). However, only higher CD45RA⁺ Treg percentage in the graft favorably impacted EA as well as nonrelapse mortality and overall survival. Our study demonstrates a critical role for CD45RA⁺ Tregs in determining EA and outcome after PTCy-based haploidentical peripheral blood stem cell transplantation, and the age-related physiologic decline in this population might be responsible for adverse impact of donor age.     

Homeostatic γδ T Cell Contents Are Preserved by Granulocyte Colony-Stimulating Factor Priming and Correlate with the Early Recovery of γδ T Cell Subsets after Haploidentical Hematopoietic Stem Cell Transplantation

Emerging evidence from graft manipulations and immunotherapeutic treatments has highlighted a favorable effect of γδ T cells in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT). However, γδ T cell subsets and their distinct features in the allograft have not been characterized. Additionally, whether homeostatic γδ T cell fractions are influenced by treatment with granulocyte colony-stimulating factor (G-CSF) remains elusive. We initially compared the phenotypes of γδ T cell subsets, including CD27⁺, CD27^-, Vδ1⁺, Vδ2⁺, Vδ1⁺CD27⁺, Vδ1⁺CD27^-, Vδ2⁺CD27⁺, and Vδ2⁺CD27^- cells, in the peripheral blood of 20 healthy donors before and after G-CSF mobilization. The effects of G-CSF on the cytokine production capacities of γδ T cell subsets were also detected. Moreover, the correlation between donor homeostatic γδ T cell content and the early recoveries of γδ T cell subgroups after haploidentical HSCT was investigated in 40 pairs of donors and recipients. We found that both the proportions and IFN-γ secretion capacities of peripheral γδ T cell subsets were preserved in G-CSF–primed grafts. Homeostatic Vδ1 and Vδ2 proportions of donors significantly correlated with the early recoveries of Vδ1 and Vδ2 cells after haploidentical HSCT. Interestingly, a higher day 30 Vδ1 concentration was associated with a lower incidence of cytomegalovirus reactivation in recipients. These results not only clarify the preservation of γδ T cell phenotypes and functional features by G-CSF mobilization but also suggest the importance of homeostatic γδ T cell content for immune recovery after alloHSCT.     

Calcineurin Inhibitor–Free Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide and Brief-Course Sirolimus Following Reduced-Intensity Peripheral Blood Stem Cell Transplantation

Calcineurin inhibitors (CNIs) form the foundation of current graft-versus-host disease (GVHD) prophylaxis regimens. We hypothesized that a CNI-free regimen consisting of post-transplantation cyclophosphamide (PTCy) and brief-course sirolimus would reduce chronic GVHD and nonrelapse mortality (NRM) after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation (PBSCT). Twenty-six patients (median age, 61 years) underwent unmanipulated PBSCT from an 8/8 locus-matched donor (matched related donor, n = 17; natched unrelated donor, n = 9). GVHD prophylaxis consisted of PTCy and brief-course sirolimus. Donor engraftment occurred in all patients. The cumulative incidence (CI) of grade II-IV acute GVHD, grade III-IV acute GVHD, and chronic GVHD was 46%, 15%, and 31% respectively. One-year NRM was 4%. The median time to immunosuppression discontinuation was day +138. With a median follow-up of 20 months, the estimated 2-year overall survival was 71%, estimated disease-free survival was 64%, and estimated relapse incidence was 32%. In patients with a lymphoid malignancy (eg, chronic lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease), 2-year disease-free survival was 100%, and there were no relapses. Good immune reconstitution was evidenced by low cytomegalovirus reactivation rate of 21% (4 of 19 at-risk patients). GVHD prophylaxis with PTCy and sirolimus achieves consistent donor engraftment, low rates of chronic GVHD and NRM, and excellent outcomes in recipients of HLA-identical related and unrelated donor allogeneic PBSCT.     

Killer Cell Immunoglobulin-Like Receptor–Ligand Mismatch in Donor versus Recipient Direction Provides Better Graft-versus-Tumor Effect in Patients with Hematologic Malignancies Undergoing Allogeneic T Cell–Replete Haploidentical Transplantation Followed by Post-Transplant Cyclophosphamide

We evaluated the impact of unidirectional donor versus recipient killer cell immunoglobulin-like receptor (KIR)–ligand mismatch (KIR-Lmm) on the outcomes of T cell–replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a cohort of 144 patients treated for various hematologi diseases. We separately analyzed 81 patients in complete remission (CR group) and 63 with active disease (no CR group) at the time of Haplo-SCT. One-third of patients in each group had KIR-Lmm. In the no CR group, KIR-Lmm was associated with a significantly lower incidence of relapse (hazard ratio, .21; P?=?.013) and better progression-free survival (hazard ratio, .42; P?=?.028), with no significant increase in graft-versus-host disease incidence or nonrelapse mortality. In contrast, in the CR group no benefit of KIR-Lmm was observed. Our results encourage considering KIR-Lmm as an additional tool to improve donor selection for T cell–replete Haplo-SCT with PT-Cy, especially in patients with high-risk diseases.     

Novel View on Umbilical Cord Blood and Maternal Peripheral Blood—an Evidence for an Increase in the Number of Circulating Stem Cells on Both Sides of the Fetal–Maternal Circulation Barrier

Umbilical cord blood (UCB) is a rich source of stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitors cells (EPCs), and very small embryonic-like stem cells (VSELs). These cells most likely are mobilized into UCB in response to hypoxia and delivery stress. We have hypothesized that they may play a role in repairing certain tissue/organ injuries that occur in the newborn child after delivery. Here we asked whether delivery also mobilizes stem cells into maternal blood, as the mother also experiences hypoxia and several types of internal tissue injuries, particularly in the reproductive tract. We observed that the number of HSCs, MSCs, EPCs, and VSELs increases in maternal blood at 24 h after physiological delivery (n?=?17). Based on this observation, we propose that delivery stress is associated with an increase in the number of circulating stem cells, not only on the fetal side but also on the maternal side of the fetal–maternal circulatory barrier.     

Graft Monocytic Myeloid-Derived Suppressor Cell Content Predicts the Risk of Acute Graft-versus-Host Disease after Allogeneic Transplantation of Granulocyte Colony-Stimulating Factor–Mobilized Peripheral Blood Stem Cells

Myeloid-derived suppressor cells (MDSCs) are powerful immunomodulatory cells that in mice play a role in infectious and inflammatory disorders, including acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Their relevance in clinical acute GVHD is poorly known. We analyzed whether granulocyte colony-stimulating factor (G-CSF) administration, used to mobilize hematopoietic stem cells, affected the frequency of MDSCs in the peripheral blood stem cell grafts of 60 unrelated donors. In addition, we evaluated whether the MDSC content in the peripheral blood stem cell grafts affected the occurrence of acute GVHD in patients undergoing unrelated donor allogeneic stem cell transplantation. Systemic treatment with G-CSF induces an expansion of myeloid cells displaying the phenotype of monocytic MDSCs (Lin^low/negHLA-DR⁻CD11b⁺CD33⁺CD14⁺) with the ability to suppress alloreactive T cells in vitro, therefore meeting the definition of MDSCs. Monocytic MDSC dose was the only graft parameter to predict acute GVHD. The cumulative incidence of acute GVHD at 180 days after transplantation for recipients receiving monocytic MDSC doses below and above the median was 63% and 22%, respectively (P = .02). The number of monocytic MDSCs infused did not impact the relapse rate or the transplant-related mortality rate (P > .05). Although further prospective studies involving larger sample size are needed to validate the exact monocytic MDSC graft dose that protects from acute GVHD, our results strongly suggest the modulation of G-CSF might be used to affect monocytic MDSCs graft cell doses for prevention of acute GVHD.     

Relationship of BK Polyoma Virus (BKV) in the Urine with Hemorrhagic Cystitis and Renal Function in Recipients of T Cell–Depleted Peripheral Blood and Cord Blood Stem Cell Transplantations

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell–depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10⁷ copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10⁷ copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria.