Allogeneic Transplant Patients Research Articles

The nursing of circumferential mixed hemorrhoids with infection during hematopoietic stem cell transplantation

Objective To summarize the nursing experience of allogeneic hematopoietic stem cell transplantation patients with circumferential mixed hemorrhoid intercurrent infection, explore the nursing methods of severe circumferential mixed hemorrhoid before allogeneic hematopoietic stem cell transplantation. Methods The detailed nurse plan and carefully observation and assess of lesion were performed daily. Iodophor water at the concentration of 0.5‰ was used for anal bath and 2% iodine ointment was used to smear perianal to prevent of infection. And gauzes soaked iodophor were used to cover the lesions, and Chinese traditional herb for anal bath and ultraviolet exposure to control infection. Additionally, the necessary psychological support was given to overcome the fear. Results After the careful nursing, the patient passed through the agranulocytosis period and achieved the success of transplantation. Conclusions This case suggests that the methods in prophylaxis of patients with circumferential mixed hemorrhoids is effectious. Key words: Hematopoietic stem cell transplantation; Nursing care; Circumferential mixed

The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of ≤12 months.

Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of ≤12months (80% and 42% at 3years, P<0·015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting.

Global Use of Peripheral Blood vs Bone Marrow as Source of Stem Cells for Allogeneic Transplantation in Patients With Bone Marrow Failure.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many patients with bone marrow failure.1 Bone marrow was initially the only stem cell source available until the 1990s when peripheral blood stem cells (PBSCs) and cord blood began to be used. Currently, PBSCs are the major stem cell source,2 owing to faster engraftment and ease of collection despite a higher rate of graft-vs-host disease and lower survival rates in patients with nonmalignant disorders.

Outcomes of Allogeneic Transplantation in Patients Aged ≤ 60 Years with Acute Myeloid Leukemia in Second Complete Remission: A CIBMTR ® Cohort Analysis

Introduction: Allogeneic hematopoietic cell transplantation (HCT) has demonstrated survival benefit in younger patients with intermediate/high-risk acute myeloid leukemia (AML), while data for older patients transplanted in CR2 in particular are limited. The purpose of the presented study was to retrospectively investigate within the CIBMTR database parameters that influence post-transplant outcome for patients aged ≥60 undergoing allogeneic HCT for AML in CR2.Methods: Using the CIBMTR database, patients aged ≥60 years with AML in CR2 who underwent HCT between 2001 and 2012 were identified. A number of patient, disease and transplant-related variables were analysed, and outcomes studied included overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM).Results: Intotal, 196 patients with AML in CR2 met the eligibility criteria for this study. Median follow-up of survivors was 73 (6-123) months. Median age at transplant was 64 years (range 60-78), 81 patients (41%) were female. Seventy one percent had a Karnofsky performance status ≥90%. De novo AML was diagnosed in 147 patients (75%). Concerning cytogenetics at diagnosis (SWOG/ECOG), 16 patients (8%) were favorable, 133 (68%) were intermediate and 17 (9%) were unfavorable risk, while 30 patients (15%) had missing data. Concerning duration of CR1, 48 patients (24%) demonstrated <6 months, 48 patients (24%) 6-12 months and 74 patients (38%) ≥12 months, missing data in 26(13%). Myeloablative conditioning regimens were used in 37 patients (19%). Fifty-eight patients (30%) had matched sibling donors, 99 (51%) were well-matched unrelated and 39 (20%) were partially matched unrelated. Peripheral blood stem cells were used in 171 patients (87%), 58 patients (30%) received in vivo T-cell depletion.Univariate analysis demonstrated a 3-year OS of 42% (95% confidence intervals [CI] 35-49), LFS of 37% (95% CI 30-44), NRM of 25% (95% CI 19-32), and CIR of 38% (95% CI 31-45). Cumulative incidence of acute GvHD at 100 days was 33% (95% CI 26-40) while chronic GvHD at 3-years was 54% (95% CI 46-61).Cytogenetics was the only independent risk factor (relative risk [RR] 1.14 (95% CI 0.59-2.19) and 2.32 (95% CI 1.05-5.14) for intermediate and unfavorable risk respectively) for survival in multivariate analysis. For CIR, cytogenetic risk was the predominant prognostic factor (RR 1.10 (95% CI 0.47-2.56) and 2.98 (95% CI 1.11-8.00) for intermediate and unfavorable risk respectively, p=0.008). A higher NRM was observed with bone marrow graft source (RR 2.75, p=0.002) and male gender (RR 2.04, p=0.02).Conclusion: This study demonstrates the potential of long-term remissions with HCT in selected older patients with AML in CR2. Patients with adverse risk cytogenetics had very poor outcome due to higher risk of post-transplant relapse, and novel strategies are required for these patients. DisclosuresGupta:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

Encouraging Outcomes in African-American Patients with Use of Post-Transplant Cyclophosphamide after HLA Mismatched Hematopoietic Stem Cell Transplant

An inherent difficulty in performing allogeneic transplantation in patients (pts) of African American (AA) descent is finding suitably matched 8/8 unrelated donors. In addition for complicated reasons studies have shown that AA have an inferior survival compared to suitable matched patients from different ethnic groups undergoing allogeneic transplantation. Post transplant cyclophosphamide (PTCy) administered on day + 3 and +4 given in combination with tacrolimus and mycophenolate mofetil (MMF) allows for the safe use of more mismatched transplants, including haploidentical transplants. This has created a new approach for patients who lack suitable donors and may allow more AA pts to proceed to transplant. At our institution, we have used PTCy as graft-versus-host-disease (GVHD) prophylaxis in patients undergoing reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) from mismatched related and unrelated donors, and this group consisted largely of high-risk AA pts.We retrospectively reviewed 16 pts who underwent HLA mismatched HSCT (5/10 to 8/10 HLA matches) at our institution between July 2012 and 2015. All patients received RIC HSCT with PTCy (days +3 and +4) along with tacrolimus and MMF for GVHD prophylaxis. Patients did not routinely receive growth factor support. Primary endpoints included time to neutrophil and platelet engraftment, length of hospital stay, and rates of acute and chronic GVHD. Secondary outcomes included time to relapse, transplant related mortality, and overall survival.Table 1 shows the demographics of the 16 patients who were transplanted. The median age of the patients was 57 years (range: 25-72). Ten pts were of AA descent. Fifteen donors were haploidentical family donors; 6 were 5/10 matches, 4 were 6/10 matches, and 5 were 7/10 matches. One patient received a 8/10 unrelated donor transplant. Five patients had failed previous transplants which included 3 allogeneic and 2 autologous HSCT. Based on published risk stratification (Armand et al. Blood, 2012) of the remaining 11 pts, 7 pts were high risk and 4 were intermediate risk. Neutrophil engraftment (first of 3 days when ANC was ³500 cells/mm3) occurred a median of 19 days post transplant (range:12-22 days); Platelet engraftment (³20,000/µL without platelet transfusion) occurred a median of 21.5 days post-transplant (range: 14-37 days). Median length of hospitalization was 26 days (range: 22-81 days). Two pts failed to engraft after first HSCT. One of these pts had high levels of anti-HLA antibodies directed against her donor. Both pts went on to a second haploidentical transplant and engrafted their neutrophil counts at 13 days and 21 days; respectively. Grade II acute GVHD occurred in 6/16 patients. No patient developed grade III-IV aGVHD. Chronic GVHD was observed in 8/16 patients with severe chronic GVHD seen in one patient. With a median follow up of 160 days (range: 89-778 days) the Kaplan-Meier estimates of overall survival at one year were 81.3% for all transplanted pts (Figure 1) and 80% for the AA pts (Figure 2). Three pts died; 1 patient from an invasive fungal infection and 2 pts from relapse. One additional patient relapsed but continues on treatment.Our experience suggests that the use of PTCy permits HLA mismatched transplantation, with overall survival of > 80% and acceptable rates of acute and chronic GVHD. Moreover, the severity of acute GVHD in patients who received PTCy post-transplant was limited, with no reported acute grade III-IV GVHD. In addition, the early outcomes of HLA mismatched transplantation in 10 African-American patients, a population that is often underrepresented in the donor registry, suggests that this approach may preferentially benefit AA pts from an expanded donor pool derived from utilization of partially HLA-matched donors. [Display omitted] [Display omitted] [Display omitted] DisclosuresLum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding.

Prognostic Impact of Peripheral Blood Count Recovery and Cytogenetic Remission Prior to Reduced Intensity Allogeneic Transplantation in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Background:Morphologic complete remission (CR) is the gold standard for assessing response in acute myelogenous leukemia (AML). CR with incomplete count recovery (CRi) and CR with incomplete platelet recovery (CRp) are associated with inferior overall survival post induction therapy (Walter et al, JCO 2010 and Chen et al, JCO 2015). Furthermore, residual cytogenetic disease is associated with a higher relapse compared with patients with cytogenetic CR (CCR; Chen et al, JCO 2011). There is a paucity of literature regarding the impact of CRi, CRp and CCR prior to allogeneic transplantation.Aim:To study the impact of CRi, CRp and CCR and their impact on relapse incidence (RI), non-relapse mortality (NRM) and overall survival (OS) in reduced intensity allogeneic stem cell transplantation (RIC-SCT).Methods:After due IRB approval, patients (pts) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who received RIC-SCT at our institution between 2008-2014 were identified. All clinical and pathologic data were retrospectively extracted. CR, CRi, CRp and CCR were defined in accordance to the international working group definition. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon/Kruskal-Wallis, respectively. Survival estimates were calculated using the kaplan-meier and log-rank test. RI was estimated on a competing event analysis using Grey's model. Cox proportional regression was used to compute hazard ratios (HR).Results:A. Baseline characteristics: A total of 134 patients were identified. A total of 70 (52%) were in CR, 40 (30%) in CRi and 24 (18%) in CRp. 129 patients had evaluable cytogenetic data pre-SCT; 81 (63%) were in CCR and 48 (37%) had persistent cytogenetic disease. Baseline patient, disease and transplant characteristics stratified by peripheral count recovery pre-SCT are shown (Table 1). Significantly more patients in CR had higher KPS, higher proportion AML diagnosis, more likely to be in first complete remission (CR1), higher rate of cytogenetic CR and a higher proportion of minor ABO mismatched donor. No other significant variables were identified between the three cohorts.B. Transplant outcomes: Median follow up of the entire cohort was 41.9 months and the 2-yr OS, RI and NRM were 61.7%, 25.7% and 21.9%. Patients in CR, CRi and CRp had a similar 2-year rates of RI (26.3%, 18.4% and 28.9%, respectively; p = 0.66), 2-year NRM (20.5%, 38.8% and 22.1%, respectively; p = 0.18) and 2-year OS (61.8%, 55.1% and 58.6%, respectively; p = 0.82). RI was significantly lower for patients in CCR pre-SCT with HR 0.25 (95% CI 0.11-0.51 p = 0.0001) without a difference in overall survival HR 0.68 (0.41-1.15; p = 0.14). However, we observed a similar RI in CR, CRi and CRp patients who had persistent cytogenetic disease pre-SCT (p = 0.55). The outcome remained similar between strata after excluding MDS patients (data not shown).Conclusion: We observed equivalent post-transplant outcomes between CR, CRi and CRp despite the presence of persistent cytogenetic disease. This suggests that RIC SCT had a role in mitigating the negative prognosis associated incomplete hematologic recovery. These findings have implications as physicians may not need to postpone SCT to await count recovery. This important question should be further validated in a larger cohort of patients. [Display omitted] [Display omitted] [Display omitted] DisclosuresAl-Kali:Novartis: Research Funding.

Donor-Derived CIK Cell Infusion As Consolidative Therapy after Non-Myeloablative Allogeneic Transplant in Patients with Myeloid Neoplasms

Introduction: Non-myeloablative conditioning combining total lymphoid irradiation (TLI) with rabbit anti-thymocyte globulin (ATG) has been shown to have a low incidence of non-relapse mortality (NRM) for patients with myeloid neoplasms (Benjamin Biol Blood Marrow Transplant 2014). As with other reduced intensity conditioning regimens, relapse remains the primary cause of treatment failure following allo-HCT using TLI-ATG conditioning. Cytokine induced killer (CIK) cells derived from peripheral blood culture with interferon (IFN)-γ, interleukin (IL)-2, and anti-CD3, have demonstrated anti-tumor effects in vitro, and have been safely administered in a phase I/II study of patients with post-transplant relapse with low incidence of acute GVHD (Laport Biol of Blood and Marrow Transplantation 2011). In an effort to promote conversion to full donor chimerism and reduce the risk of relapse following TLI/ATG conditioning for patients with myeloid neoplasms, we evaluated the addition of donor derived cytokine induced killer (CIK) cells post-HCT.Methods: Here we report interim results for 37 patients enrolled to date in an unplanned analysis. Day+90 full donor chimerism (FDC) was the primary endpoint. Secondary endpoints include overall survival and incidence of acute GVHD. Median age is 64 years (range 37-74) with primary disease of de novo MDS (19, 51.3%), secondary AML (6, 16.2%), MPN (2, 5.4%), and therapy (t-) related myeloid neoplasm (10, 27%; including 4, t-MDS; 4, t-AML; 2, t-MDS/MPN overlap). Of patients with MDS or MDS/MPN overlap, 54% had intermediate-2 IPSS risk classification. Fifteen (40.5%) patients had a morphological complete remission at the time of HCT. Twenty-three (62%) donors were unrelated.Results: Median CD34+ dose was 7.2e6/kg (range 2.3-17e6/kg). Ten patients (27%) did not receive CIK cells; causes included CD34+ cell dose below the threshold for culture inoculation (n=4), acute graft versus host disease (n=2), fever with concern for active infection at the time of scheduled infusion (n=1), or logistical reasons (n=3, including lack of donor consent for CIK infusion, transplant delay, and reagent unavailability). Of the 27 patients receiving CIK cells, 23 received the target dose of 1e8/kg CD3+ CIK product, at a median time of 26 days (range 24-31) post peripheral blood stem cell (PBSC) infusion. The median CD3+, CD3+CD56+, CD3+CD8+NKG2D+, CD8+CD45RO+ cell culture content was 97%, 13%, 51%, and 41%, respectively. Median followup time for living patients is 420 days. Day+90 FDC, defined by 95% or greater donor-type peripheral blood CD3+ cells, was 29%. The incidence of acute GVHD grade II-IV and grade III-IV in the total cohort is 21.6% and 5.4%, respectively. The incidence of chronic GVHD is 19%. Of the 27 patients receiving CIK product, the incidence of acute GVHD grade II-IV is 7.4% with no acute grade III or IV events to date and 22% chronic GVHD.On an intention to treat analysis of enrolled patients, one year NRM 10.5% (95% CI: 0.8%-22.1%) and one year cumulative incidence of relapse 46.3% (95% CI: 28.4%-64.1%) are not significantly different compared to our historical cohort (5.2%, 95%CI: 2.0%-8.4% and 53%, 95%CI: 45.9%-60.1%) respectively. The 1-year OS by intention to treat of 68.6% (95%CI: 54%-87%) is similar to our historical control, 60.8% (95%CI: 54.3%-68.2%, p=0.76). The 1-year OS in the 27 CIK recipients is 75% (95%CI: 59.3%-94.7%).Conclusion: CIK infusion was found to be safe and feasible. There was no increase in grade III-IV acute GVHD or chronic GVHD risk. There was a statistically non-significant trend towards increased one-year survival in our cohort. The potential benefit on overall survival remains to be further evaluated with additional patient enrollment and longer followup. However, given the favorable safety profile of CIK cells, future strategies to enhance efficacy such as repeat dosing or modification of CIK cells are worth potential exploration. DisclosuresBenjamin:Amgen, Inc.: Employment, Equity Ownership. Rezvani:Pharmacyclics: Research Funding.

The Association of Gilbert's Syndrome with Hyperbilirubinaemia Occurring on Any of Imatinib, Dasatinib and Nilotinib in Patients with Chronic Myeloid Leukaemia (CML)

Background: Individuals with Gilbert's syndrome present with mild, unconjugated hyperbilirubinaemia, resulting from impaired glucuronidation by reduced uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression. The A(TA)7TAA polymorphism responsible for the syndrome has been associated with nilotinib-induced hyperbilirubinaemia in patients with chronic myeloid leukaemia (CML). Our study extends UGT1A1 molecular analysis to a larger cohort of CML patients receiving other tyrosine kinase inhibitors (TKIs) and explores the relationship with other abnormalities of liver function.Methods: We interrogated our database of 832 patients treated with a TKI for CML at our center and identified 467 individuals who presented in first chronic phase, who had received only a TKI (prior interferon, combination experimental therapy, autologous and allogeneic transplant patients were all excluded) and for whom serial liver function results were available. We then performed PCR to identify variations in dinucleotide repeats in the UGT1A1 promoter region. Genotypes were assigned as follows: 6/6 (homozygous for (TA)6 allele; wild-type), 7/7 (homozygous for (TA)7allele) and 6/7 (heterozygous). Because individual patients may have received more than one TKI, we defined the period on treatment with each TKI as an 'episode' in order to be able to attribute abnormalities of liver function to a specific drug. Hyperbilirubinaemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Both ALT and ALP were defined as increased if they were above the upper limit of normal. To date we have completed the analysis for 340 patients comprising a total of 568 episodes of TKI therapy (imatinib 313, dasatinib 125, nilotinib 130).Results: The UGT1A1 genotype analysis showed six variants. The majority of patients displayed one of 6/6 (149 patients), 6/7 (138 patients) or 7/7 (48 patients) genotypes. Small numbers of patients with the 5/6, 5/7 and 6/8 genotypes were excluded from further analysis. Hyperbilirubinaemia was seen in patients with all three genotypes, but was more frequent in patients on nilotinib (44%), compared to imatinib (14%) and dasatinib (8%). The incidence of hyperbilirubinaemia in individuals with the 6/6 genotype was 6%, 0% and 22% for imatinib, dasatinib and nilotinib respectively, and 10%, 6% and 56% for patients with the 6/7 genotype. The frequency of hyperbilirubinaemia in those with the 7/7 genotype was significantly higher compared to the occurrence of such events in any other genotype, irrespective of treatment. However, it occurred more often in patients on nilotinib (80%), followed by imatinib (61%) and dasatinib (44%). A significantly higher number of patients with the 7/7 genotype on nilotinib reported Grade 3 hyperbilirubinaemia (25%), with no grade 3 events on imatinib and only one on dasatinib. Hyperbilirubinaemia on any single drug did not predict for this event on any subsequent drug.Further analysis of liver function tests (LFTs) and bilirubin levels divided episodes into four groups: 1. Episodes with normal bilirubin and normal LFTs (n = 273), 2. Episodes with isolated raised LFTs but normal bilirubin (n = 179), 3. Episodes with isolated hyperbilirubinaemia (n = 27) but normal LFTs and 4. Episodes with raised bilirubin and raised LFTs (n = 84). Abnormal LFTs with or without hyperbilirubinaemia were most commonly seen on nilotinib (65%) compared to imatinib (40%) and dasatinib (46%), confirming previous reports of the frequencies of transaminitis on the various TKIs. Isolated hyperbilirubnaemia was uncommon (<6%) on any of the drugs, but was more frequent in the 7/7 than the 6/6 or 6/7 genotypes for imatinib or dasatinib. Interestingly it was not seen in patients with the 7/7 genotype on nilotinib, as 80% of the 7/7 patients with hyperblirubinaemia on nilotinib had other abnormalities of liver function.Conclusion. We confirmed the increased risk of hyperbilirubinaemia in individuals with the A(TA)7TAA polymorphism when treated with nilotinib. In contrast to other reports, we found that all patients with the 7/7 genotype are susceptible to increases in bilirubin when treated with any of imatinib, dasatinib or nilotinib. Hyperbilirubinaemia most commonly occurs alongside elevations in LFTs on nilotinib, indicating a nilotinib-induced hepatotoxicity that is compounded by the additional UGT1A1 inhibition. DisclosuresMilojkovic:ARIAD Pharmaceuticals Inc.: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Apperley:Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Ariad: Honoraria; Novartis: Honoraria. Foroni:Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Ariad: Research Funding.

HO-1-Transduced Mesenchymal Stem Cells Attenuate aGVHD By Inhibiting HIF-1α /ROR-γt and then Down-Regulate Proportion of TH17/Treg

Background. In acute graft versus host disease, the balance pattern of Treg/Thl7 cells are destroyed, leading to a series of inflammation and damage to the body, greatly affect the survival of allogeneic hematopoietic stem cell transplantation patients. Mesenchymal stem cells can regulate the body's balance of TH17/Treg cells, clinically used to prevent and treat aGVHD.But between immune adjustment ability of mesenchymal stem cells in clinical trials have not been shown to efficiently prevent and treatment of GVHD. HO - 1 as a significant anti-inflammatory and immunosuppressive molecules in rats and human MSC played a crucial role in immune suppression function.In this article, we discuss slow virus in mice mediated transfection MSC HO-1 key nuclear transcription factor can inhibit the TH17 STAT3 activation to further decline, the proportion of TH17/Treg and whether more effectively adjust the related the secretion of cytokines to alleviate aGVHD caused by inflammation of the target organ damage, in addition to observe the clinical patients undergoing allogeneic transplantation patients occurred aGVHD HO-1 high expression and the relationship between the expression of STAT3 and the secretion of peripheral blood serum of TH17/Treg related factors.Methods.Lentivirus transfection raised for rat mesenchymal stem cells between the expression of HO-1, trailing edge vein injection of mice treated, fluorescence microscopy MSC colonize the target organs of mice, pathological biopsy to detect target organ damage, immunohistochemical detection of target organs and the spleen and the expression of pSTAT3, HO-1 flow cytometry to detect the spleen, drainage of lymph node ratio of TH17/Treg cells, Realtime PCR and ELISA to detect the related inflammatory factor levels.Results. The mouse in accepting HO-1 high expression of mesenchymal stem cells after infusion, significantly reduce aGVHD, immunohistochemical results show that the main target organs damage in the expression of HO-1 is inversely proportional to the expression of STAT3 and spleen pSTAT3 protein and total level of STAT3 protein was lower than other groups, the spleen and lymph nodes of TH17/Treg proportion are lower than other groups, IL-17 A, ROR-ϒt mRNA level and serum concentration is lower than other groups, FOXP3, TGF-β mRNA and serum concentration is higher than in the rest of the group.Conclusions. These results suggest that activation of HO - 1 May improve the anti-inflammatory and immune suppression ability of MSC, and perhaps by inhibiting the phosphorylation of STAT3, cut ratio of TH17/Treg cells, promote reduce aGVHD. DisclosuresNo relevant conflicts of interest to declare.

Reduced Intensity Continuous Infusion Busulfan for Allogeneic Hematopoietic Cell Transplant Patients with Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment with a More Intensive Therapeutic Regimen: LCCC 0306

Background: A major advance in allogeneic stem cell transplant (SCT) has been the establishment of effective and less toxic reduced intensity regimens as alternative therapeutic approaches for patients with certain hematologic malignancies. The focus of these approaches has been to reduce treatment related mortality (TRM) while providing sufficient host immunosuppression to permit the achievement of complete donor chimerism that leads to a graft versus tumor effect, resulting in long-term disease control and cure. In this study we report overall survival (OS), relapse rate (RR), and non-relapse mortality (NRM) in patients receiving reduced intensity conditioning (RIC) with a 48 hour continuous infusion of busulfan with fludarabine followed by methotrexate (MTX) alone or with lympho-depleting anti-CD52 monoclonal antibody (mAb), alemtuzumab, or T cell depleting immunoglobulins, anti-thymocyte globulin (ATG) given as graft versus host disease (GVHD) prophylaxis.Methods: Patients with histologically confirmed hematologic malignancies, who were over the age of 55, or otherwise ineligible for more intensive busulfan-based therapy were enrolled on a Phase II protocol, LCCC 0306, at the University of North Carolina. All patients received IV fludarabine 30 mg/m2/day on days-7 through-3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days-6 through-5 and tacrolimus from day-1 plus either MTX alone, ATG or alemtuzumab alone, or a combination of these agents depending on disease risk and donor status.Results: 71 patients were enrolled. The median age was 58 (range 28 - 69). 58% were men and 42% women. 37 patients received HLA-matched related donor (MRD) stem cell grafts, and 34 patients received either matched unrelated donor (MUD) or HLA-mismatched grafts. The median HCT-Comorbidity Index (CI) score was 3 (range 0 - 8, HCT-CI score: 0 = 12 pts, 1 - 2 = 22 pts, ⪴ 3 = 36 pts). The majority of pts were intermediate risk by Disease Risk Index (DRI) score (9 low, 40 int, 19 high, 1 very high, 2 undetermined). The DRI low/int group had an estimated 18 month OS of 65% (CI 0.50 - 0.77), and DRI high/very high OS was 35% (CI 0.16 - 0.55). Estimated median survival time based on DRI for low/int was 1674 days (CI 646 - 2920) versus 375.5 days (CI 136 - 1018) (p = 0.003) for DRI high/very high pts. OS at 18 months in the MTX alone arm (n = 20) was 70% (CI 0.45 - 0.83), ATG (+/- MTX, n = 27) was 52% (CI 0.32 - 0.69), and alemtuzumab (+/- MTX, n = 24) was 46% (CI 0.26 - 0.64); (p = 0.17). The 18 month relapse rate for the MTX alone arm was 50% (CI 0.27 - 0.69), 41% in ATG (CI 0.37 - 0.76), and 41% in alemtuzumab (CI 0.36 - 0.77); (p = 0.85). The 18 month NRM in the MTX alone arm was 7% (CI 0.61 - 0.99), alemtuzumab (+/- MTX) was 32% (CI 0.42 - 0.85), and ATG (+/- MTX) was 27% (CI 0.52 - 0.86); (p = 0.05). Much of the increased NRM in the alemtuzumab and ATG arms was attributable to increased rates of fatal infectious complications: 1 in the MTX arm, 3 in the ATG arm and 8 in the alemtuzumab arm. No patients receiving MTX alone, 3 receiving alemtuzumab and 6 receiving ATG developed grade 3-4 acute GVHD. 5 of the 20 surviving patients have extensive chronic GVHD.Conclusion: Continuous infusion, reduced dose, busulfan and fludarabine can be safely administered to patients who are ineligible for myeloablative conditioning either because of age or comorbidities. The use of MTX alone with this regimen results in a median survival of over 4 years. Patients with high DRI or who received treatment with alemtuzumab or ATG had higher NRM and poorer OS irrespective of donor status. DisclosuresWood:Best Doctors: Consultancy; Inform Genomics: Consultancy.

Analysis of Impact of Comorbidities Constituting the HCT-CI Score on the Outcome of Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia

The Hematopoietic Cell Transplant Co-morbidity Index (HCT-CI, Sorror et al 2005) was developed as a prognostic tool for overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic cell transplant (HCT) patients. The prognostic significance of the score for patients with acute myeloid leukemia (AML) undergoing HCT has been demonstrated, however reports are conflicting. The purpose of this single-center study was to retrospectively investigate the prognostic impact of the individual component co-morbidities of the HCT-CI on the outcome of 418 patients that underwent HCT for AML at our center between 2000 and 2013.Patients underwent HCT in first (CR1, n=303) and second (CR2, n=115) complete remission. Median age at HCT was 50 years (range 18-71), 212 (51%) patients were female. Myeloablative conditioning (MAC) was used in 283 (68%) patients, reduced-intensity (RIC) in 135 (32%) patients. Donors were related for 236 (56%) patients, unrelated for 182 (44%) patients. Grafts were peripheral blood stem cells (PBSC) in 339 (81%) patients and bone marrow in 79 (19%) patients. Median follow-up of patients alive was 62 months (range 12-168). Cytogenetics at diagnosis were available for 84% of patients, of which 31 (7%) were favorable, 246 (59%) were intermediate and 74 (18%) were unfavorable risk (MRC classification). HCT-CI scores were grouped as 0 (n=109, 26%), 1-2 (n=157, 38%) and ≥3 (n=152, 36%). A total of 171 patients (41%) underwent HCT during the years 2000-2006 and 247 patients (59%) during the years 2007-2013. The observed frequency of the co-morbidities composing the HCT-CI is summarized in Table 1.Univariate analysis for OS demonstrated the following significant variables: Age (HR=1.02, 95%CI=1.01-1.03, p=0.0002), CR status (HR=1.42 for CR2, 95%CI=1.08-1.87, P=0.01), donor type (HR=0.73 for related, 95%CI=0.57-0.94, p=0.02), HCT-CI group (overall p-value=0.004). For OS, univariate analysis of the impact of individual co-morbidities was performed for the components of the HCT-CI score that were observed in ≥5% of the patients (Table 1). All variables with a p-value ≤0.2 were introduced into the multivariable analysis (not including the HCT-CI itself), and these included cardiac disorder (CAD, CHF, MI or EF≤50%) (HR=1.65, 95%CI=1.17-2.32, p=0.004), prior solid tumor (HR=1.56, 95%CI=1.06-2.30, p=0.02) and diabetes (HR=1.40, 95%CI=0.89-2.19, p=0.14). In the multivariable analysis for OS, none of the aforementioned co-morbidities demonstrated independent prognostic relevance. For NRM, univariate analysis demonstrated cardiac disorder (HR=1.89, 95%CI=1.27-2.81, p=0.002), diabetes (HR=1.94, 95%CI=1.20-3.12, p=0.007) and moderate pulmonary (FEV1 and/or DLCO 66-80% or dyspnea on slight activity) (HR=1.31, 95%CI=0.93-1.84, p=0.12) to meet the significance criteria for inclusion in the multivariable analysis, which finally demonstrated diabetes (HR=2.17, 95%CI=1.31-3.60, p=0.003) and cardiac disorder (HR=1.78, 95%CI=1.15-2.76, p=0.01) to be independent predictors of NRM post-transplant.In conclusion, among the pre-transplant co-morbidities included in the HCT-CI, diabetes and cardiac dysfunction are independent prognostic indicators for NRM but not for OS. Pulmonary dysfunction does not seem to negatively influence outcomes in this cohort of patients. [Display omitted] DisclosuresKim:Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

Use of Post-Transplant Cyclophosphamide (PTCy) with Mycophenolate Mofetil and Tacrolimus in HLA Matched Allogeneic Hematopoietic Cell Transplant Is Safe and Associated with Acceptable Transplant Outcomes

Background: The use of post-transplantation cyclophosphamide (PTCy) as a single agent for graft-versus-host disease (GVHD) prophylaxis in HLA matched transplant patients has had varied results. Two recent studies at Johns Hopkins University noted favorable incidences of both GVHD and non-relapse mortality (NRM) in both matched related and unrelated donor allogeneic hematopoietic cell transplant (allo-HCT) recipients (Kanakry CG, et al, JCO, 2013 and Kanakry CG et al, Blood, 2014). In contrast to this data, a phase II study at MD Anderson reported higher rates of grade II-IV acute GVHD and NRM, with worse overall survival in patients receiving PTCy as the sole GVHD prophylaxis compared to their matched cohort receiving a calcineurin-inhibitor (CNI) and methotrexate (MTX) as immunosuppression (Alousi AM et al, BBMT, 2015). Another study in Australia had to be stopped for safety reasons due to high GVHD and NRM when using PTCy as sole GVHD prophylaxis (Bradstock KF, BBMT, 2015). There is no published data on the use of MMF plus tacrolimus in combination with PTCy in HLA matched allo-HCT recipients. We hypothesized that addition of MMF and Tacrolimus to PTCy in HLA matched allo-HCT recipients will lead to significantly improved transplant outcomes. To answer this question we retrospectively analyzed data from patients who received this regimen at a single institution.Methods. We performed a retrospective analysis of 31 HLA matched allo-HCT patients who received PTCy at 50 mg/m2 on days +3 and +4 in addition to MMF and tacrolimus immunosuppression from December 2012 till June 2015 at Washington University School of Medicine in Saint Louis. All of these patients received G-CSF mobilized peripheral blood grafts. Patients included AML (n=13), ALL (n=5), MDS (n=5), CML (n=2), aplastic anemia (n=2) and NHL (n=1), myelofibrosis (n=1). Twelve of the patients underwent a matched related donor (MRD) transplant and 19 underwent a matched unrelated donor (MUD) transplant. Two of the MUD transplants had a HLA match grade of 8 of 10 and the other 17 were a 10 out of 10 match. Twenty-eight of the patients received a graft collected via peripheral blood stem cell mobilization and the other three had a donor graft collected via bone marrow harvest. Cumulative incidence of aGVHD was estimated using Gray's sub-distribution method to account for death without aGVHD as a competing event, and the cumulative incidences of non-relapse mortality (NRM) and relapse were estimated treating each other as competing event, while OS was estimated using Kaplan-Meier limit method.Results: This regimen was associated with acceptable GVHD in our patients. Incidence of grade II-IV acute GVHD was 28% (21.3% for MRD; 31.5% for MUD) at day 100 and 28% at 1 year. Incidence of Grade III-IV acute GVHD was 13.5% at both 100 days and 1 year. Limited chronic GVHD was 25.9% and extensive GVHD was 14.8% at 1 year. Similarly we found acceptable NRM and relapse in these patients, NRM was 10.2% and 19.7% at 100 days and 1 year respectively and cumulative incidence of relapse at 100 days and 1 year were 17.8% and 29.0% respectively. Overall survival at 1 year for all patients was 52%.Summary: Here we report favorable results from a regimen combining MMF and Tacrolimus on PTCy platform in HLA matched MRD and MUD transplant recipients. Relatively low GVHD and NRM results are particularly encouraging in view of almost exclusive use of G-CSF mobilized T cell replete grafts with much higher T cell content. Though limited by the relatively small number of patients, our results suggest combining MMF plus Tacrolimus with PTCy platform in HLA matched allogeneic transplant patients is safe and associated with acceptable transplant outcomes. DisclosuresVij:Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; BMS: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Merck: Consultancy. Uy:Novartis: Research Funding. Abboud:Teva Pharmaceuticals: Research Funding; Gerson Lehman Group: Consultancy; Merck: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Schroeder:Celgene: Other: Azacitidine provided for this trial by Celgene; Incyte: Consultancy. Jacoby:Sunesis: Research Funding; Novo Nordisk: Consultancy.

Embedding palliative care into bone marrow transplantation clinic.

157 Background: Stem cell/bone marrow transplantation (SC/BMT) is intensive therapy that creates the potential for a number of physical and emotional symptoms. Despite the symptom burden and support needs of these patients there are no publications describing palliative care involvement in the course of treatment. Methods: Retrospective chart review was performed on 37 patients followed over a 6-month period by a palliative care service embedded within the SC/BMT clinic. Results: 37 patients were referred by SC/BMT clinic physicians or nurses to a palliative care team embedded within the clinic (including a physician, physical therapist, and psychologist). Almost all patients were referred for symptom management rather than goals of care; only three (9%) died during the review period and for none of them was the reason for consultation goals of care/hospice referral. Patients were seen between once and eight times during the six month period by various members of the team. Most (77%) were allogenic transplant patients and most were seen within 6 months of their transplantation. The most common reasons for referral were fatigue (57%), anorexia (27%), pain (38%) and depression and/or anxiety (35%). At initial assessment the highest-rated symptoms were lack of appetite (mean 4.78, SD 3.08), fatigue (4.51 [2.59]), and diminished feeling of well-being (4.16, [2.51]). At initial assessment, 73% of patients had 3 or more different symptoms that they rated at 4+; this dropped to 39.1% at follow-up (n = 23). Of the 9 symptoms assessed at both initial and follow-up visits, 7 decreased significantly (all but fatigue and dyspnea) and none increased. For example appetite improved from 5.52 (2.98) to 3.13 (2.96); pain improved from 3.52 (2.92) to 1.78 (1.88) (n = 23, p &lt; .01). SC/BMT providers requested an expansion of the service after three months of experience. Conclusions: Patients who have undergone SC/BMT experience many physical and emotional symptoms. Palliative care embedded within the bone marrow transplant clinic can provide benefit by lessening the symptomatic burden of patients.

Allografting versus Autografting for Follicular Lymphoma: An Ongoing Conundrum.

It has been more than 2 decades since the initial reports on autologous transplantation for follicular lymphoma [1,2]. These studies were paradigm changing because they provided the first evidence of a curative therapy in this chronically relapsing illness. However, autologous transplantation was effective in only a fraction of carefully selected patients with chemotherapy-sensitive disease. Relapse rates were high, possibly caused by infusion of occult lymphoma cells [3]. Therapy-related myelodysplastic syndrome/acute myeloid leukemia, mostly occurring in the first 5 years after transplant, emerged as a considerable problem, attributable to conditioning, to prior treatment, and possibly to stem cell mobilization method [4,5]. Allogeneic transplantation was soon found to have a very low incidence of disease recurrence but also a high early mortality [6]. Three prior studies have compared autologous and allogeneic transplantation with consistent conclusions: allogeneic transplantation has much higher treatment-related mortality, regardless of conditioning intensity, but lower rates of recurrence [7-9]. In this issue, Klyuchnikov et al. [10] address the same issue again, from a somewhat different angle: They include only patients with prior exposure to rituximab, only allo-transplants undergoing reduced-intensity conditioning, and limit their analysis to patients with follicular grades I and II disease. They find that allogeneic transplant recipients tend to have more advanced disease, die much more frequently from complications, and relapse less. Patients with high lactate dehydrogenase and poor

Adverse Events During Hematopoietic Stem Cell Infusion: Analysis of the Infusion Product.

Stem cell transplantation is a treatment option for patients with cancer. However, a risk of adverse events might be associated with the infusion itself. An understanding of the types and grades of adverse events occurring during infusion and the patient and infusion characteristics that might be associated with these events could allow for interventions to minimize these complications. The risk factors associated with transplant-related adverse events are not well understood. We retrospectively analyzed the adverse events occurring within 1 hour after infusion in 460 patients with cancer undergoing stem cell transplantation at the Northwestern University Robert H. Lurie Comprehensive Cancer Center from January 1, 2008 and May 1, 2011. Of the 460 patients, 382 received autologous transplants and 78 allogeneic transplants. The incidence, types, and National Cancer Institute Common Terminology Criteria grade of toxicity for adverse events were noted (primary objective). Univariate analyses were performed to study which patient and infusion characteristics might be associated with the occurrence of adverse events (secondary objectives). Of the 460 patients, 261 (56.7%) experienced adverse events (66.7% during allogeneic infusion and 54.7% during autologous infusion). Most events were cardiopulmonary. Univariate analysis of the infusion and patient characteristics revealed that a second transplant (P= .005) was associated with more adverse events for autologous transplant patients. For allogeneic transplant patients, a higher infusion red blood cell volume (P= .01) was associated with more adverse events. Adverse events are common during stem cell infusion and are generally cardiopulmonary.

The study of myocardial protective effect of creatine phosphate sodium in liver transplant patients

Objective: To study the cardioprotective effectof creatine phosphate sodium by measuring perioperative myocardial enzymes of allogeneic liver transplant patients. Methods: The 26 cases of orthotopic liver transplant patients were randomly divided into control group and creatine phosphate sodium group, 13 cases in each group. The creatine phosphate sodium group were given creatine phosphate sodium 30 mg/kg at the time of induction. The control group were given equal amount of N.S. All patients at six-phase of before surgery, after anesthesia,before anhepatic phase, anhepatic phase,new liver and the 12 hours after surgery extraction radial artery. The CK, CK-MB and cTnI activity was measured. Results: To compared with control group, creatine phosphate sodium group’s plasma CK, CK-MB and cTnI concentrations in before anhepatic phase, anhepatic phase, new liver and the 12 hours after surgery 4 phase are significantly lower ( p&lt;0.05). Conclusions: The creatine phosphate sodium has a protective effect on liver transplantation in patients with myocardial damage.

The study of myocardial protective effect of creatine phosphate sodium in liver transplant patients

Objective: To study the cardioprotective effectof creatine phosphate sodium by measuring perioperative myocardial enzymes of allogeneic liver transplant patients. Methods: The 26 cases of orthotopic liver transplant patients were randomly divided into control group and creatine phosphate sodium group, 13 cases in each group. The creatine phosphate sodium group were given creatine phosphate sodium 30 mg/kg at the time of induction. The control group were given equal amount of N.S. All patients at six-phase of before surgery, after anesthesia,before anhepatic phase, anhepatic phase,new liver and the 12 hours after surgery extraction radial artery. The CK, CK-MB and cTnI activity was measured. Results: To compared with control group, creatine phosphate sodium group’s plasma CK, CK-MB and cTnI concentrations in before anhepatic phase, anhepatic phase, new liver and the 12 hours after surgery 4 phase are significantly lower ( p&lt;0.05). Conclusions: The creatine phosphate sodium has a protective effect on liver transplantation in patients with myocardial damage.

Delays in Intensification are Common in Adults with Acute Lymphoblastic Leukemia (ALL), are Associated with Decreased Survival in Allogeneic Hematopoietic Cell Transplant (HCT) Patients

Delays in Intensification are Common in Adults with Acute Lymphoblastic Leukemia (ALL), are Associated with Decreased Survival in Allogeneic Hematopoietic Cell Transplant (HCT) Patients

İntestinal graft versus host hastalığının endoskopik bulgularının retrospektif değerlendirilmesi

Background and Aims: Acute graft-versus-host disease occurs after allogeneic hematopoietic stem cell transplantation and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells. About 35%-50% of hematopoietic stem cell transplant recipients will develop acute graft-versus-host disease. The endoscopic findings varied markedly and included mild mucosal edema with focal erythema, diffuse erythema, and diffuse polypoid indurations with multiple bleeding ulcerations. We investigated endoscopic findings in a graft-versus-host disease patient population. Materials and Methods: A retrospective review of endoscopic data was performed in 18 adult allogeneic bone marrow transplant recipients at our institution. Results: In this study, 18 allogeneic bone marrow transplant patients (mean age 33.9 years; 62% male) were evaluated. In 6 graftversus- host disease patients, the endoscopic appearances of the esophagus, stomach and duodenum varied from subtle mucosal erythema and edema to frank ulceration. Colonoscopy was performed with biopsies in 12 graft-versus- host disease patients. The colonoscopic findings varied markedly and ranged from mild mucosal edema with focal erythema to multiple bleeding ulcerations. Conclusions: The diagnostic accuracy of endoscopy was high in gastrointestinal graft-versus-host disease. Accurate diagnosis of gastrointestinal graft-versus-host disease might be obtained with mucosal biopsies from either the upper or lower gastrointestinal tract. Endoscopy may play a significant role in establishing early diagnosis and treatment for gastrointestinal graft-versus-host disease patients.

Mixed Donor Chimerism after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome

Mixed Donor Chimerism after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome