A Prospective Study to Evaluate Efficacy Using the Nuro Percutaneous Tibial Neuromodulation System in Drug-Naïve Patients With Overactive Bladder Syndrome.

OBJECTIVE: To evaluate changes from baseline in urgency urinary incontinence episodes, urinary frequency and quality of life through 12 weeks of percutaneous tibial neuromodulation (PTNM) therapy using NURO in drug-naïve overactive bladder syndrome (OAB) subjects. METHODS: Eligible subjects underwent 12 weekly PTNM sessions with the NURO system. Changes in voiding symptoms were evaluated with bladder diaries from baseline through 12 weeks. Analyses were conducted for subjects with data at baseline and follow-up visits (sessions 1, 4, 8, and 12). Safety was evaluated through adverse events (AE) related to the device, procedure, and therapy. RESULTS: Of 154 subjects enrolled in the study,120 subjects met study criteria and received PTNM. The mean age was 64.8 years, mean duration of OAB diagnosis was 3.4 years and 86% female subjects. No subjects tried OAB medication prior to enrollment. At baseline, patients had 3.5 ± 2.5 (mean ± SD) UUI episodes/day. Statistically significant improvement in urgency urinary incontinence episodes from baseline was observed at each follow-up visit (P < .0001), with a reduction of 2.4 ± 2.1 episodes after session 12 from baseline. Subjects with urinary frequency at baseline had 11.5 ± 2.9 voids/day. After session 12, a statistically significant reduction of 1.7 ± 2.5 voids/day was observed (P < .0001). Ninety-six percent (116/120) of subjects completed the study with diary data for the primary objective with an average of 11.6 sessions. There were no serious or unanticipated AEs. The most common AEs were medical device site pain (3.3%, 4/121) and extremity pain (3.3%, 4/121). CONCLUSION: PTNM using NURO is an effective and safe treatment for drug-naïve patients with OAB.

Baseline symptom severity and therapeutic success in a large prospective trial of sacral neuromodulation therapy for overactive bladder patients.

INTRODUCTION: The InSite trial is a prospective, multicenter post-approval study of subjects receiving sacral neuromodulation (SNM) therapy with the InterStim® System. Enrolled subjects had bothersome symptoms of overactive bladder (OAB). The purpose of this analysis was to determine if severity of baseline symptoms had an impact on clinical outcomes. METHODS: For device implant, therapeutic success was defined as a ≥50% improvement in average leaks/day, or in voids/day or a return to normal voiding frequency. Groups were dichotomized into less versus more severe based on median number of leaks and voids. Subjects were grouped as less severe <2 leaks/day for UI; <11 voids/day for UF and more severe ≥2 leaks/day for UI; ≥11 voids/day for UF. Therapeutic success at 12 and 24 months were compared between groups. RESULTS: Three hundred and forty subjects completed test stimulation and 272 (80%) subjects received a full system implant. On average UI subjects had 1.3 leaks/day in the less severe group and 4.5 leaks/day in the more severe group. UI success rates were not statistically different between severity groups at 12 months or 24 months). At baseline, on average UF subjects had 9.4 voids/day for the less severe group and 15.1 voids/day for the more severe group. UF success rates were not statistically different between severity groups at 12 months or 24 months. CONCLUSION: Data evaluating efficacy based on symptom severity demonstrates that SNM is effective in treating both less severe and more severely affected groups for both UI and UF at 12 and 24 months.

Five-Year Followup Results of a Prospective, Multicenter Study of Patients with Overactive Bladder Treated with Sacral Neuromodulation.

PURPOSE: We evaluated the therapeutic success rate, changes in quality of life and safety of sacral neuromodulation 5 years after InterStim™ implantation. Included in study were subjects with bothersome symptoms of overactive bladder, including urinary urge incontinence and/or urgency-frequency, in whom at least 1 anticholinergic medication failed and 1 medication had not been tried. MATERIALS AND METHODS: Therapeutic success was defined as a urinary urge incontinence or urgency-frequency response of 50% or greater improvement in average leaks or voids per day, or return to normal voiding, defined as fewer than 8 voids per day. Quality of life was evaluated by ICIQ-OABqol (International Consultation on Incontinence Modular Questionnaire). Safety was evaluated through adverse events. RESULTS: Of the 340 subjects who completed the test stimulation 272 had an implant, of whom 91% were female. Mean age was 57 years. At baseline 202 subjects with urinary urge incontinence had a mean ± SD of 3.1 ± 2.7 leaks per day and 189 with urgency-frequency had a mean of 12.6 ± 4.5 voids per day. The 5-year therapeutic success rate was 67% (95% CI 60-74) using modified completers analysis and 82% (95% CI 76-88) using completers analysis. Subjects with urinary urge incontinence had a mean reduction from baseline of 2.0 ± 2.2 leaks per day and subjects with urgency-frequency had a mean reduction of 5.4 ± 4.3 voids per day (each completers analysis p <0.0001). Subjects showed improvement in all ICIQ-OABqol measures (p <0.0001). The most common device related adverse events were an undesirable change in stimulation in 60 of the 272 subjects (22%), implant site pain in 40 (15%) and therapeutic product ineffectiveness in 36 (13%). CONCLUSIONS: This multicenter study shows that sacral neuromodulation had sustained efficacy and quality of life improvements, and an acceptable safety profile through 5 years in subjects with overactive bladder.

Prospective Randomized Feasibility Study Assessing the Effect of Cyclic Sacral Neuromodulation on Urinary Urge Incontinence in Women.

OBJECTIVES: The aim of this prospective, randomized, multicenter, single-blind, 4 × 4 crossover study was to estimate the effect of 4 InterStim cycling settings (continuous, 16 seconds on/8 seconds off, 10 minutes on/10 minutes off, and 30 minutes on/23.5 hours off) on efficacy, Global Response Assessment, and safety. METHODS: Eligible women implanted for at least 3 months for urgency urinary incontinence (UI) were enrolled, and daily diaries were collected. General linear mixed models were used to estimate the cycling effect on efficacy. Quality of life measured by Global Response Assessment (subjects' perception of effectiveness) and safety were summarized. RESULTS: Primary efficacy analysis was based on the first 24 subjects who completed unique randomization sequences. Mean age was 64 years, and mean implant duration was 2.8 years. Results showed no significant cycling (P = 0.3773) or period (P = 0.0800) effect on UI. There was a statistically significant interaction between cycling and period (P = 0.0032). In the first period, subjects on 10 minutes on/10 minutes off had significantly fewer UI episodes compared with subjects on 16 seconds on/8 seconds off (P = 0.0026); this difference was not observed in any other period or sensitivity analyses. No cycling effect was found on urgency or pad usage. When programmed to 10 minutes on/10 minutes off, 54% of subjects felt their incontinence symptoms improved compared with when they entered the study, followed by 42% on 30 minutes on/23.5 hours off, 38% on 16 seconds on/8 seconds off, and 29% on continuous. Safety was similar across cycling settings. CONCLUSIONS: The results suggest that patients with overactive bladder who have been implanted with sacral neuromodulation devices and are receiving substantial benefit may perceive further optimization by switching to cycling settings.

Three-year Follow-up Results of a Prospective, Multicenter Study in Overactive Bladder Subjects Treated With Sacral Neuromodulation.

OBJECTIVE: To evaluate the therapeutic success rate, and changes in quality of life (QOL) and safety in subjects using sacral neuromodulation (InterStim System) at 36 months. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) and/or urgency frequency (UF), who had failed at least 1 anticholinergic medication, and had at least 1 untried medication were included. METHODS: Subjects with successful test stimulation received an InterStim implant. Therapeutic success and quality of life through 36 months was evaluated in implanted subjects with data at baseline and follow-up. Safety was evaluated using reported adverse events. RESULTS: A total of 340 subjects received test stimulation resulting in 272 implanted subjects. Demographics include 91% female, mean age of 57 years, and baseline symptom severity of 3.1 ± 2.7 leaks/day (UI) and 12.6 ± 4.5 voids/day (UF). The analysis showed an OAB therapeutic success rate of 83% (95% confidence interval: 78%-88%). UI subjects had a mean reduction from baseline of 2.3 ± 2.3 leaks/day whereas UF subjects had a mean reduction of 5.3 ± 4.0 voids/day (both P < .0001). Statistically significant improvements were observed in all measures of the International Consultation on Incontinence Modular Questionnaire-OABqol (all P < .0001). Eighty percent of subjects reported improvements in their urinary symptom interference. Device-related adverse events occurred in 47% (127/272) of subjects post-implant; 91% were resolved at the time of this analysis. CONCLUSION: The 36-month follow-up data from the multicenter study demonstrate sustained safety, effectiveness, and improved QOL in subjects implanted with InterStim, without requiring failure of all medications.

Results of a prospective, multicenter study evaluating quality of life, safety, and efficacy of sacral neuromodulation at twelve months in subjects with symptoms of overactive bladder.

AIMS: This prospective, multicenter post-approval study evaluated the success rate of sacral neuromodulation (SNM) with the InterStim® System at 12-months. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) or urgency-frequency (UF), who failed at least one anticholinergic medication and had at least one not tried were included. METHODS: Subjects with successful test stimulation received an SNM implant. Therapeutic success (≥50% improvement in average leaks/day or voids/day or a return to normal voiding frequency [<8 voids/day]) and quality of life through 12 months were evaluated for implanted subjects. RESULTS: Of the 340 subjects that went through test stimulation, 272 were implanted with SNM. Of these, 91% were female, mean age was 57, UI subjects had 3.1 ± 2.7 leaks/day, UF subjects had 12.6 ± 4.5 voids/day. The analysis which includes all implanted subjects with diary data at baseline and 12 months showed an OAB therapeutic success rate of 85% at 12 months. UI subjects had a mean reduction of 2.2 ± 2.7 leaks/day; UF subjects had a mean reduction of 5.1 ± 4.1 voids/day (both P < 0.0001). Subjects showed significant improvement from baseline in all measures of ICIQ-OABqol (all P < 0.0001). 80% of subjects reported improved changes in their urinary symptom interference at 12 months. Device-related adverse events occurred in 16% (56/340) of subjects during test stimulation and 30% (82/272) of subjects post-implant. CONCLUSIONS: This multicenter study shows SNM is safe and effective and results in improved outcomes through 12 months in subjects with OAB symptoms, without requiring failure of all medications.

Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6-months in subjects with mild symptoms of overactive bladder.

AIMS: This prospective, randomized, multicenter trial evaluated the 6-month success rate of sacral neuromodulation (SNM) with InterStim® Therapy versus standard medical therapy (SMT) for overactive bladder (OAB). METHODS: Enrolled subjects discontinued OAB medications prior to and during baseline data collection and were randomized 1:1 to SNM or SMT. Subjects had bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (≥2 leaks/72 hr) and/or urgency-frequency (≥8 voids/day). Subjects failed at least one anticholinergic medication, and had at least one medication not yet attempted. The primary objective was to compare OAB therapeutic success rate at 6 months between SNM and SMT. RESULTS: Overall, 147 subjects were randomized (70 to SNM and 77 to SMT); 93% were female and mean age was 58. The primary intent to treat analysis showed OAB therapeutic success was significantly greater in the SNM group (61%) than the SMT group (42%; P = 0.02). In the as treated analysis, OAB therapeutic success was 76% for SNM and 49% for SMT (P = 0.002). The SNM group showed significant improvements in quality of life versus the SMT group (all P < 0.001) and 86% of SNM subjects reported improved or greatly improved urinary symptom interference score at 6 months, compared to 44% for SMT subjects. The device-related adverse event rate was 30.5% and the medication-related adverse event rate was 27.3%. CONCLUSIONS: This study demonstrates superior objective and subjective success of SNM compared to SMT. SNM is shown to be a safe and effective treatment for OAB patients with mild to moderate symptoms. Neurourol. Urodynam. 34:224-230, 2015. © 2014 Wiley Periodicals, Inc.

Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer?

Older patients are increasingly undergoing allogeneic hematopoietic transplantation. A relevant question is whether outcomes can be improved with a younger allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD). Accordingly, transplants in leukemia/lymphoma patients age ≥50 years were analyzed comparing outcomes for recipients of MSD ≥50 (n = 1415) versus MUD <50 years (n = 757). Risks of acute graft-versus-host disease (GVHD) grade 2 to 4 (hazard ratio [HR], 1.63; P < .001), 3 to 4 (HR, 1.85; P < .001), and chronic GVHD (HR, 1.48; P < .0001) were higher after MUD compared with MSD transplants. The effect of donor type on nonrelapse mortality (NRM), relapse, and overall mortality was associated with performance score. For patients with scores of 90 or 100, NRM (HR, 1.42; P = .001), relapse (HR, 1.45; P < .001), and overall mortality (HR, 1.28; P = .001) risks were higher after MUD transplants. For patients with scores below 90, NRM (HR, 0.96; P = .76), relapse (HR, 0.86; P = .25), and overall mortality (HR, 0.90; P = .29) were not significantly different after MUD and MSD transplants. These data favor an MSD over a MUD in patients age ≥50 years.

Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia.

UNLABELLED: Cell dose is a major limitation for umbilical cord blood (UCB) transplantation because units containing a minimum of 2.5 x 10(7) total nucleated cells (TNC)/kilogram patient body weight are frequently not available. The transplantation of 2 partially HLA-matched UCB units has been adopted as a simple approach for increasing the TNC.We sought to determine whether the relative safety and efficacy of this approach was comparable with a single UCB transplantation. Included are adults with acute leukemia who received transplants with 1 (n =106) or 2 (n =303) UCB units. All UCB units for single UCB transplantations contained TNC ≥ 2.5 x 10(7)/kg. For double UCB transplantations, the total TNC for units 1 and 2 were > 2.5 x 10(7)/kg but in approximately half of these transplantations, 1 of the 2 units contained < 2.5 x 10(7) TNC/kg. Adjusting for factors associated with outcomes, risks of neutrophil recovery (odds ratio 0.83, P =.59), transplantation-related mortality (hazard ratio [HR] 0.91, P= .63), relapse (HR 0.90, P= .64), and overall mortality (HR 0.93, P= .62) was similar after double UCB and adequate dose single UCB transplantations. These data support double UCB unit transplantation for acute leukemia when an adequately dosed single UCB unit is not available thereby extending access to nearly all patients. KEY POINTS: Efficacy of transplanting adequately dosed 1- or 2-cord blood units.

Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes.

We report the relative efficacy of co-infusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophosphamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine ± TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor.

Donor characteristics affecting graft failure, graft-versus-host disease, and survival after unrelated donor transplantation with reduced-intensity conditioning for hematologic malignancies.

We examined the effect of donor characteristics on graft failure (<5% donor chimerism within 3 months after transplantation), acute and chronic graft-versus-host disease (aGVHD, cGVHD), and survival after unrelated donor reduced-intensity conditioning (RIC) transplantation in 709 patients with hematologic malignancies. Donor-recipient pairs were HLA typed at HLA-A, -B, -C, and -DRB1 (allele-level). A total of 501 patients were >95% donor chimerism, 145 patients were 5% to 95%, and 63 patients were <5%. The only donor characteristic associated with transplantation outcome was donor-recipient HLA matching. One- or 2-loci mismatched transplants led to higher grade 2-4 (relative risk [RR] = 1.27, P = .035) and grade 3-4 (RR = 1.85, P < .001) aGVHD and 2-loci mismatched transplants higher mortality (RR = 2.22, P < .001). Graft failure was higher after transplantation of bone marrow (RR = 2.33, P = .002). Donor age, parity, and donor sex match were not associated with transplantation outcome. Donor-recipient HLA matching is the only donor characteristic predictive for survival after RIC regimens for hematologic malignancies.

Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti-T-cell antibody infusion abrogates the therapeutic benefits of transplantation. We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 antithymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell- replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell- replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell-replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell-replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens.

The outcomes of family haploidentical hematopoietic stem cell transplantation in hematologic malignancies are not associated with patient age.

Haploidentical hematopoietic cell transplantation (HCT) has been used to treat hematologic malignancies, but it is unknown whether the procedure is more effective in adults or children. To address this question, we analyzed patients aged 1 to 65 years old receiving myeloablative conditioning regimens followed by family 2 to 3 antigen HLA-mismatched HCT and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR; n = 137) or performed in Dao-Pei Hospital in China, China (n = 181). The Dao-Pei cohort had more acute and chronic graft-versus-host disease (GVHD), less relapse, lower transplant-related mortality (TRM), and better leukemia-free survival (LFS) than the CIBMTR cohort. Overall survival (OS) and outcomes were similar between adults and children. In the CIBMTR cohort receiving ex vivo T cell depletion (TCD), adults had higher TRM (relative risk [RR] 2.71, 95% confidence interval [CI] 1.29-5.69, P = .008) and lower OS (RR 1.75, 95% CI 1.08-2.84, P = .023) than children. In the CIBMTR subset that did not receive ex vivo TCD, relapse was lower in adults compared to children (RR 0.24, 95% CI 0.07-0.80, P = .020), but TRM, LFS, and OS were similar. We conclude that outcomes in adults and children are similar overall, although children have better survival than adults if ex vivo TCD is used.

Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia.

We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.

One-antigen mismatched related versus HLA-matched unrelated donor hematopoietic stem cell transplantation in adults with acute leukemia: Center for International Blood and Marrow Transplant Research results in the era of molecular HLA typing.

Approximately 13% of patients lacking an HLA-identical sibling have a one-antigen-mismatched related donor (MMRD). Historically, outcomes from the use of a one-antigen MMRD were considered equivalent to those from the use of a matched unrelated donor (UD). Recent improvements in UD stem cell transplantation (SCT) resulting from better molecular HLA matching justifies investigating whether UD should be preferred over MMRD in adult patients with acute leukemia. Here, we compared the outcomes of MMRD (n = 89) and HLA-A, -B, -C, and -DRB1 allele-matched UD (n = 700) SCT reported to the Center for International Blood and Marrow Transplant Research between 1995 and 2005. The patients underwent transplantation for acute myelogenous leukemia or acute lymphoblastic leukemia in first or second complete remission. Donor type was not associated with hematologic recovery. Univariate and multivariate comparisons of MMRD versus HLA-matched UD transplants showed no statistically significant differences in overall survival, disease-free survival, treatment-related mortality, relapse, or 100-day grade III-IV acute graft-versus-host disease (GVHD). MMRD SCT was associated with a lower rate of chronic GVHD at 1 year (35% vs 47%; P = .03), which was confirmed by multivariate analysis (relative risk, 0.58; 95% confidence interval, 0.39-0.85; P < .01). According to our data, HLA-matched UD and MMRD SCT are associated with comparable survival. Given that less chronic GVHD was observed in the MMRD transplantations, this option, when available, remains the first choice in patients with acute leukemia without an HLA-identical sibling in need of allogeneic SCT.

Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.

Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

The effect of the composition of unrelated donor bone marrow and peripheral blood progenitor cell grafts on transplantation outcomes.

To test the hypothesis that the outcome of hematopoietic stem cell (HSC) grafts is at least partially determined by the cellular composition of the graft, the National Marrow Donor Program (NMDP) analyzed the correlation of cellular phenotypes of unrelated grafts with graft outcome. Samples from 94 bone marrow (BM) and 181 peripheral blood progenitor cell (PBPC) grafts for transplantations at 40 U.S. transplant centers between 2003 and 2005 were analyzed at a single immunophenotyping reference laboratory. Samples were shipped from transplant centers upon receipt of graft. Graft cellular composition included analysis of leukocyte total cell numbers, and subsets of myeloid [CD34(+), CD34(+) CD38(-)], lymphoid [CD3(+), CD3(+) CD4(+), CD3(+) CD8(+)], and activated lymphoid cells [CD3(+) CD25(+), CD3(+) CD69(+), CD3(+) HLA-DR(+)] coexpressing CD3(+). There was substantial variability in the cellular composition of BM and PBPC grafts before and after graft processing by red blood cell (RBC) removal or plasma depletion in preparation for transplant. With BM grafts, cellular composition was not associated with hematopoietic recovery, graft-versus-host disease (GVHD), or survival. With PBPC grafts, survival rates were higher with CD34(+)>5 x 10(6)/kg, 59% compared to 34% with CD34(+)< or =5 x 10(6)/kg at 1 year. Platelet recovery was higher with PBPC containing CD3(+) CD8(+) >8 x 10(7)/kg. Neutrophil recovery or GVHD could not be predicted by any cellular subsets of PBPC grafts. Although survival was superior with PBPC grafts containing >5 x 10(6) CD34(+)/kg, an optimal graft mix of myeloid, lymphoid, and activated lymphoid subsets was not identified.

Rapid transport and infusion of hematopoietic cells is associated with improved outcome after myeloablative therapy and unrelated donor transplant.

We evaluated effects of graft transport time on outcomes after transplantation of 938 unrelated donor bone marrow (BM) or 507 peripheral blood progenitor cells (PBPC) in patients with acute or chronic leukemia and myelodysplastic syndrome (MDS). BM grafts were collected at 107 centers and PBPC, 89 centers. Median time from end of collection to infusion was 14 hours for BM and 15 hours for PBPC. Platelet recovery was less likely in BM recipients when the interval from end of collection to receipt at transplant center was >or=20 hours (odds ratio 0.47, P = .010) and when the interval from receipt to infusion was >or=6 hours (odds ratio 0.57, P = .001). Mortality rates were higher in recipients of HLA-matched BM when the interval from end of collection to receipt at transplant center was >or=20 hours (relative risk 2.67, P < .001) after adjustment for other significant prognostic factors. Mortality after HLA-mismatched BM transplants was not associated with transport time. Transport times had no demonstrable effect on outcomes after PBPC transplants. These data support a general review of current transport procedures, especially for BM grafts requiring longer transport time and every effort made to minimize time from collection to infusion.

HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation.

The National Marrow Donor Program maintains a registry of volunteer donors for patients in need of a hematopoietic stem cell transplantation. Strategies for selecting a partially HLA-mismatched donor vary when a full match cannot be identified. Some transplantation centers limit the selection of mismatched donors to those sharing mismatched antigens within HLA-A and HLA-B cross-reactive groups (CREGs). To assess whether an HLA mismatch within a CREG group ("minor") may result in better outcome than a mismatch outside CREG groups ("major"), we analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem cell transplantations. Three-hundred and ninety-six pairs (15%) were HLA-DRB1 allele matched but had an antigen-level mismatch at HLA-A or HLA-B. Univariate and multivariate analyses of engraftment, graft-versus-host disease, and survival showed that outcome is not significantly different between minor and major mismatches (P = .47, from the log-rank test for Kaplan-Meier survival). However, HLA-A, HLA-B, and HLA-DRB1 allele-matched cases had significantly better outcome than mismatched cases (P < .001). For patients without an HLA match, the selection of a CREG-compatible donor as tested does not improve outcome.