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Ending homelessness among veterans has been a goal of the Department of Veterans Affairs for some time, and it is now becoming a reality in many communities. Unprecedented strides have been made through the rapid implementation of evidence-based innovations, capacity building, and a comprehensive strategic focus on 4 goals: prevention, moving veterans into permanent housing, providing the population-tailored care and services needed to keep them housed, and providing the supports necessary to allow them to recover and be productive members of their communities.

Introduction Although the clinical consequences of homelessness are well described, less is known about the role for health care systems in improving clinical and social outcomes for the homeless. We described the national implementation of a “homeless medical home” initiative in the Veterans Health Administration (VHA) and correlated patient health outcomes with characteristics of high-performing sites. Methods We conducted an observational study of 33 VHA facilities with homeless medical homes and patient- aligned care teams that served more than 14,000 patients. We correlated site-specific health care performance data for the 3,543 homeless veterans enrolled in the program from October 2013 through March 2014, including those receiving ambulatory or acute health care services during the 6 months prior to enrollment in our study and 6 months post-enrollment with corresponding survey data on the Homeless Patient Aligned Care Team (H-PACT) program implementation. We defined high performance as high rates of ambulatory care and reduced use of acute care services. Results More than 96% of VHA patients enrolled in these programs were concurrently receiving VHA homeless services. Of the 33 sites studied, 82% provided hygiene care (on-site showers, hygiene kits, and laundry), 76% provided transportation, and 55% had an on-site clothes pantry; 42% had a food pantry and provided on-site meals or other food assistance. Six-month patterns of acute-care use pre-enrollment and post-enrollment for 3,543 consecutively enrolled patients showed a 19.0% reduction in emergency department use and a 34.7% reduction in hospitalizations. Three features were significantly associated with high performance: 1) higher staffing ratios than other sites, 1) integration of social supports and social services into clinical care, and 3) outreach to and integration with community agencies. Conclusion Integrating social determinants of health into clinical care can be effective for high-risk homeless veterans.

The authors reflect on a comprehensive, evidence-based, data and outcome-driven strategy to prevent homelessness among veterans which has been developed by the U.S. Department of Veteran Affairs. They suggest that the strategy will likely lead to new public health challenges. They argue that a demand for evidence-based, outcome-driven initiatives and programs to predict the needs and manage the care of formerly homeless people will lead to additional public health research.

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34+ stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800.

Abstract 830 Haplo-cord transplant, the co-infusion of CD34+ stem cells from a haploidentical (haplo) family member with a cord blood (UCB) unit has been proposed as a method to reduce duration of pancytopenia after UCB SCT. We prospectively investigated reduced intensity conditioning (RIC) of fludarabine, melphalan and rATG followed by haplo-cord SCT in 45 patients with high-risk hematological malignancies. Thirteen patients (29%) belonged to ethnic or racial minorities, and almost half had AML. Median age was 50; weight 80 kg and twenty six (58%) had active disease at the time of transplant. The median CD34+ cell content post-selection of the haplo graft was 3.5 ×106/kg (25%–75% inter quartile range (IQR) 1.36–4.63). Minimal required UCB cell dose was 1×107 nucleated cells/kg. Median infused UCB total nucleated cell was 1.55×107 (range 1.24 to 2.09). 36 pts (80%) had at least a 5/6 matched UCB. The cumulative incidence of neutrophil recovery at day +50 was 95% (95% CI, 87–100%) with a median time to engraftment of 11 days (IQR 9 –15 days). The cumulative incidence of platelet recovery at day +100 was 83% (95% CI, 69–97%) with median time to platelet engraftment of 19 days (IQR 15–33 days). Patients received a median number of 12 platelet transfusions (IQR 6–22) and 7 red blood cell units (IQR 4–12) after the transplant. The median number of day of hospitalization during the first 100 days after transplant was 26 days (IQR 15–43 days). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB cells by 100 days. The median percentage of haploidentical cells in unfractionated peripheral blood was 86% on day 30, but declined to 22% by day 100, and to 2% by day 180. Conversely, the median percentage of cells of UCB origin increased from 10% by day 30, to 78% by day 100, and to 95% by day 180. There was also some re-emergence of host hematopoiesis over time. The percentage of day 100 haplo donor chimerism correlated closely with the CD34+ cell content of the haplo-identical graft (106/kg) (r=0.6225; P=0.0003). TNC, CD34+ cells, or CD3+ cells of the UCB did not correlate with cord donor chimerism. The cumulative incidence of acute GVHD (Grade II -IV) was 25% (95% CI 11–39). There were only two patients with chronic GVHD for a cumulative incidence of 6% at 1 year. Cumulative incidence of treatment related mortality was 9% (95% CI 1–17) at day 100 and 28% (95% CI 13–43) at one year. Cumulative incidence of disease recurrence was 11% (95% CI 3–19) at day 100 and 30% (95% CI 14–44) at one year. With a median follow up for survivors of 330 days (range 64–1259), estimated one year survival was 55% (95% CI 39–71) and progression free survival was 42% (95% CI 25–79). Active disease at the time of haplo-cord SCT tended to impair PFS, but this difference did not reach statistical significance (P=0.06). The cumulative incidence of CMV viremia was 42% (95% CI 26–58), but there were only four cases of CMV disease. The cumulative incidence of EBV viremia was 42% (95% CI 26–58%), but most cases were self limited or transient. Five patients developed biopsy or radiological proven PTLD, for a cumulative incidence of 11% (95% CI 0–22). RIC and haplo-cord transplant results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic GVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay and promising long term outcomes. UCB cell dose has no impact on time to hematopoietic recovery and UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. Disclosures: Off Label Use: Velcade in T-cell and aggressive non-MCL B-cell NHL.

Abstract 3378 Poster Board III-266 Introduction: Haploidentical-cord blood transplantation is a promising approach for patients (pts) who lack HLA donors and may improve rates of early engraftment while allowing long term cord blood reconstitution with low rates of GVHD. We enrolled 29 pts (17 AML/MDS, 4 ALL, 3 CML, 4 NHL/HL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 40 years (range, 4-67), and median weight was 75 kg (range, 14-125). Twenty-two (76%) pts had active disease at time of transplant; 6 had prior autologous transplants. 14 pts were Caucasian; 15 were other race or ethnicity. The haploidentical donor was the mother in 4; father in 3; child in 10; sibling in 10; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.51 × 106/kg (range, 1.25-10.95); CD3+ cells were 1.0 × 104/kg (range, 0.3-3.7). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 2 pts; 5/6 in 18 pts; 4/6 in 9 pts. Median cord total nucleated cells equaled 1.93 × 107/kg (range, 1.07-9.36); CD34+ cells were 0.08 × 106/kg (range, 0.03-0.75). The conditioning regimen for 18 pts was fludarabine (Flu) (30 mg/m2 on d-7 through -3), melphalan (Mel) (70 mg/m2 on d -3 and -2), and Thymoglobulin (rATG) (1.5 mg/kg on d-7, -5, -3, -1). Eleven pts received Flu, thiotepa (5 mg/kg on d -7 and -6), total-body irradiation (TBI) (12 Gy lateral opposed fields in 2 Gy fractions BID on d-3 through -1), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Engraftment: Two pts died early (sepsis, CVA). Three other pts failed to engraft with either haploidentical or CB and died of infection on d36, 43, and 63. One of these had anti-donor HLA antibodies. 24 pts engrafted with a median time to ANC >500/mL of 10 days (range, 9-31) and median time to sustained platelets >20,000/mL of 20 days (range, 15-63). In the majority of pts, early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. However, 3 pts had persistent hematopoiesis associated with only the haploidentical donor, while a fourth pt engrafted with only CB on day 31. Late graft failure and death from sepsis occurred in one of the patients with haploidentical engraftment. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0-100) on d14; 76% (range, 0-95) on d30; 6% (range, 0-87) on d100. Median unfractionated cord chimerism was Conclusions: Combined haploidentical and CB transplantation results in early haploidentical engraftment followed by durable CB predominance in a majority of pts. The median times to neutrophil engraftment are considerably shorter - and the range narrower - than with other methods of cord blood transplantation. Early haploidentical engraftment failed in four patients; cord blood engraftment also failed in three of these pts and in three others. Rates of acute and particularly of chronic GVHD are low. Durable remissions can be achieved even in high risk pts regardless of age or remission status at the time of transplant. Disclosures: Rich: Genzyme: Research Funding. Odenike:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees. van Besien:Genzyme: Research Funding.

Abstract 197 Supported by an unrestricted grant from Genzyme Corporation. Fludarabine (Flu) melphalan-alemtuzumab is a well tolerated, reduced intensity conditioning regimen for HCT. Clofarabine (Clo), a second generation nucleoside analog with excellent activity in acute leukemia, might enhance disease control over Flu. We report outcomes of a completed phase I and ongoing phase II study of CMA conditioning for allogeneic peripheral blood HCT. Tacrolimus was administered as GVHD prophylaxis. For the phase I cohort, one pt was enrolled per dose level, until the first DLT or until 2 had grade 3 toxicity. Dose level 1 consisted of: clo 10 mg/m2/day on d −7 to −3 and melphalan 100 mg/m2 on day −2. Clo was increased by 10 mg/m2/day per cohort until 40 mg/m2/day. Then, melphalan was increased by 20 mg/m2 until 140 mg/m2. Alemtuzumab was given at a fixed dose of 20 mg/day on d −7 to −3. Twelve pts were accrued in the phase I portion of whom three remain in remission at 26, 22 and 21 months. Forty pts, median age 53 (24–69), have been accrued in the phase II study of whom 16 had related and 24 unrelated donors. 20 had AML/MDS (6 refractory, 4 CR2, 9 CR1, 1 untreated MDS), 16 NHL (6 refractory, 9 chemosensitive relapse, 1 CR1) 2 CLL, 2 MPD. ASBMT risk score was high in 14, intermediate in 14, and low in 12. Performance score was 0 in 19, 1 in 17, 2 in 2, and not documented in 2 patients. The phase II dose was initiated at Clo 40 mg/m2/day x 5 days and melphalan 140 mg/m2. Twenty-four pts received this dose. Grade 3 renal toxicity occurred between day −7 and day +7 in 4 of 24 (17%) pts receiving this dose. The phase II dose was then reduced to Clo 30 mg/m2/day x 5 days and melphalan 140 mg/m2, and used to treat 16 pts. One pt with preexisting cardiomyopathy and refractory AML died during conditioning from cardiovascular failure. No grade 3 renal toxicity has been observed in this cohort and 3 pts had reversible grade 2 renal failure. Other toxicities included: gr 2–3 reversible ALT elevation between day −2 and day +5 in 8 pts; gr 2 reversible bilirubin elevation in 1 pt. No grade 3–4 hand foot syndrome or VOD occurred in this cohort. All evaluable pts engrafted. Twenty of 24 pts had full donor CD3 chimerism on day 30 and 2 had mixed donor chimerism. 11 pts had gr II aGVHD, and 3 had gr IIII/IV aGVHD. 7 have cGVHD.With a median follow-up of 313 days (19–607), 24 of 40 pts (60%) in the phase II portion of the study remain in remission. Eight have relapsed, 4 of whom have died. Eight others have died of treatment-related causes (7 after Clo 40 and 1 after Clo 30). Estimated one year survival is 72% (95%CI, 56–88) and PFS is 63% (45–81%). Neither dose of Clo (40 vs 30), donor type (MUD vs related), age (< 50 vs >50) affected outcomes. One year PFS was 56% (28–84) for NHL and 68% (46–90) for AML/MDS (P=NS). One year PFS was 43% (15–71%) for ASBMT high risk pts vs 70% (50–90%) for ASBMT low/intermediate risk pts (P=0.01; Figure 1). Conclusions: Clofarabine - melphalan - alemtuzumab conditioning induces durable remissions in a substantial fraction of patients with advanced hematologic malignancies. Clo 30/Mel 140 has an excellent safety profile. Disclosures: Off Label Use: clofarabine for transplant conditioning. Kline:Genzyme corporation: Membership on an entity's Board of Directors or advisory committees. Odenike:Genzyme corporation: Membership on an entity's Board of Directors or advisory committees. Stock:Genzyme: Research Funding.

Seventeen patients with therapy-related myelodysplastic syndrome (t- MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.

Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale–Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.