scholarly journals The Impact of Palifermin Use on Hematopoietic Cell Transplant Outcomes in Children

2016 ◽  
Vol 22 (8) ◽  
pp. 1460-1466 ◽  
Author(s):  
Wael Saber ◽  
Mei-Jie Zhang ◽  
Patricia Steinert ◽  
Min Chen ◽  
Mary M. Horowitz
Keyword(s):  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Transplant Outcomes ◽  
The Impact

Impact of Splenomegaly in the Presence of Negative PET FDG Avidity on Allogeneic Hematopoietic Cell Transplant Outcomes in Patients with Lymphoid Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5524-5524
Author(s):  
Farhad Khimani ◽  
Daniel K. Jeong ◽  
Taiga Nishihori ◽  
Ernesto Ayala ◽  
Joseph A Pidala ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Research Database ◽  
Hematopoietic Cell Transplant ◽  
Transplant Outcomes ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Lymphoid Malignancies ◽  
Advisory Boards ◽  
The Impact

Abstract Background: It is unclear if persistent splenomegaly prior to allogeneic hematopoietic cell transplant (allo-HCT) influences post-transplant outcomes for lymphoid malignancies. Our study explores the significance of splenomegaly along with splenic PET avidity and its impact on allogeneic HCT outcomes in patients with lymphoid malignancies. Methods: We retrospectively reviewed records of patients who underwent allo-HCT for lymphoid malignancies (n=152) between 2008 and 2013 at the Moffitt Cancer Center. Clinical data were captured through our research database and were supplemented with individual patient electronic medical record review. Pre-transplant CT and PET images of all patients were reviewed. Spleen volume (SV) was measured using the freehand volume segmentation tool in AW Workstation software (General Electric, Waukesha, WI, USA) on CT images. Splenic index (SI) was calculated as a product of width (W), thickness (Th) and length (L) of the spleen. Normal SV and SI was defined as SV < 314.5 cm3 and SI ≤ 480 cm3 as described in the literature. Spleen and liver mean standardized uptake value (SUV) s were calculated to document spleen PET avidity using region of interest measurements over the spleen and liver with standard radiology techniques. Spleens with mean SUV of lower value than liver were considered negative. Statistical analysis was performed using SPSS v.21.0. Results: Among the study population 42.8% received an allo-HCT from an HLA-matched related donor, 36.2% from a matched unrelated donor, 12.5% from a mismatched unrelated donor, and 8.6% received a double-umbilical cord blood transplants. Most patients (61.8%) received myeloablative conditioning. Median age at transplantation was 52(range 21-68) years. Pre-HCT spleen CT and PET images were available on 88% (n=134) and 70.3% (n=107) patients, respectively. Spleen volumes ranged from 90 cm3 to 4684 cm3 with a median of 290.5 cm3 and a mean of 400.3 cm3. SI calculation showed SI ranging from 50.3 cm3 to 8276.4 cm3 with a median of 582.1 cm3 and a mean of 771.2 cm3. Majority of patients (83.1%) had PET negative spleen pre-HCT. Stratified analysis and survival plots were obtained based on pre-transplant SV, SI and spleen PET status. The 2-year overall survival (OS) and progression-free survival (PFS) were 57.3% and 44.9%, respectively for all patients. 2-year OS and PFS for patients with SV ≥ 314.5 cm3 was 57.6% (95%CI 44.2-68.8) and 43.2% (95%CI 30.7-55.1), respectively, whereas for patients with SV < 314.5 cm3 was 58.1% (95%CI 45.8-68.5) and 48.4% (95%CI 36.4-59.3), respectively, with no significant differences in OS (p=0.82) or PFS (p=0.63). There were no differences among higher SV or SI vs. normal SV or SI in PET positive population but among PET negative group there was a suggestion of a favorable OS and PFS with normal SV and SI. (Figures 1&2). Conclusions: There were no significant associations between spleen size or spleen PET status and allo-HCT outcomes (PFS or OS) in patients with lymphoid malignancy. Sample size is limited in our study. Future studies using registry data or larger prospective studies are required to evaluate the impact of splenomegaly and its PET avidity on allo-HCT outcomes in lymphoid malignancies. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Locke: Kite Pharma: Other: Scientific Advisory Boards.

scholarly journals The Hematopoietic Cell Transplant Pharmacist: A Call to Action

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 3 ◽  
Author(s):  
Amber Clemmons
Keyword(s):  
Cellular Therapy ◽  
Pharmacy Practice ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Call To Action ◽  
American Society ◽  
State Of The Science ◽  
Available Information ◽  
The Impact

Recently, the required training and credentials for as well as the various roles of the hematopoietic cell transplant (HCT) pharmacist have been endorsed by the leading organizations in cellular therapy, the American Society of Transplant and Cellular Therapy and the European Society of Blood and Bone Marrow Transplantation. While these documents establish the roles a HCT pharmacist can fulfill within the multi-disciplinary team, few reports have evaluated the impact of the HCT pharmacist on clinical, financial, or quality outcomes. Further, a paucity of information has been reported on types of practice models, such as the use of collaborative practice agreements, or described effective methods to overcome the barriers to the increased utilization of HCT pharmacists. Herein, a brief summary of available information is provided to aid readers in understanding the state of the science for pharmacists practicing in this specialty with the goal to stimulate further research to justify the roles of HCT pharmacists and the correlation of such research to various outcome measures. Practitioners are encouraged to build upon this existing knowledge to create the novel integration and elevation of pharmacy practice to improve outcomes for patients, providers, and payors.

scholarly journals Role of Human Bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients

2020 ◽  
Author(s):  
Chikara Ogimi ◽  
Emily T Martin ◽  
Hu Xie ◽  
Angela P Campbell ◽  
Alpana Waghmare ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Hematopoietic Cell ◽  
Respiratory Pathogen ◽  
Human Bocavirus ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Tract Infections ◽  
The Impact

Abstract Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. Methods In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutchinson Cancer Research Center (2005–2010). Samples were tested by multiplex semiquantitative polymerase chain reaction (PCR) for 12 viruses. Plasma samples from BoV + subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens. Results Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (P = .04) and presence of respiratory copathogens (P = .03) were associated with presence of respiratory symptoms, but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens (incidence rate of 0.4% [9/2509] per sample tested). Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise. Conclusions BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.

Donor T Cells from B Cell Deficient Mice Inhibit B Cell Development in Normal Recipients after Hematopoietic Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3265-3265
Author(s):  
Antonia M.S. Mueller ◽  
Jessica A. Allen ◽  
David Miklos ◽  
Judith A. Shizuru
Keyword(s):  
T Cells ◽  
B Cell ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Chimerism ◽  
Donor T Cells ◽  
The Impact

Abstract Allogeneic hematopoietic cell transplant (HCT) recipients often exhibit B cell (BC) lymphopenia due, in part, to graft-versus-host-disease (GVHD). Here, we studied the impact of donor T cells (TC) on BC deficiency post minor antigen-mismatched HCT. Following lethal irradiation, BALB.B mice were given FACS purified hematopoietic stem cells (HSC: cKIT+Thy1.1loLin-Sca-1+) alone, with whole splenocytes (SP), CD4 or CD8 TC from minor antigen-mismatched C57BL/6 (B6) mice. Chimerism analyses were performed on day (d) 30, 60, and 90. When pure HSC were transplanted, BCs reconstituted promptly (median 33% of lymphocytes [d30]; 61% [d60]; 74% [d90]), whereas TC engraftment was retarded and did not achieve full donor chimerism. Addition of SP or CD4 TCs, or to a lesser degree CD8 TCs, delayed BC reconstitution, with extremely low percentages of BCs beyond d60. This BC suppression correlated with the degree of acute GVHD, and BC numbers increased with recovery from GVHD. Additionally, this BC suppression was in stark contrast to TC development, with TC transfer resulting in early conversion to full donor chimerism. To test if previous events in the donor sensitize TCs against BC features (e.g. minor antigens), thereby promoting anti-BC cytotoxicity post-HCT, TCs from B6 muMT mice were co-transplanted with HSC. muMT mice are devoid of mature BCs because they lack the mu chain; consequently, their TCs were not exposed to BCs prior to transfer. Remarkably, BC engraftment was completely prevented through d90. TCs regenerated faster, but the vast majority originated from spleen and not HSC. To differentiate this lack of BC engraftment from GVHD-associated, alloreactive BC lymphopenia, syngenic B6 recipients were used. Again, initially complete blockade of BC engraftment was observed, although this suppression was overcome earlier post-HCT as compared to the minor-mismatched pair (median % BC d60: ’HSC only’ recipients 52%; +CD4 17%; +CD8 48%). To clarify if this phenomenon was a purely cytotoxic reaction of muMT TC against BCs, we used WT B6 HSC +/− SP as donors and lethally or sublethally irradiated muMT mice as recipients. All groups, including sublethally irradiated animals, where host muMT TC were still present, engrafted BCs making a direct anti-BC cytotoxicity unlikely as the sole cause of the BC inhibition. FACS analysis of bone marrow was used to assess the developmental stages of BCs (Hardy fractions (Fr.) A-F) and revealed GVHD recipients with peripheral B lymphopenia have a shift of B220+ cells from more mature Fr. D-F to immature Fr. A-C stages and a lower proportion of IgM expressing BC. Recipients of the muMT TCs showed, in addition to a shift to more immature stages, a clear block in BC development with an absent switch to the expression of IgM (stage D to E)(Fig. 1). In conclusion, muMT TCs are capable of blocking BC maturation when transferred into WT mice, suggesting defective TC activity in muMT animals necessary for the co-development of both BCs and TCs. Furthermore, this study provides evidence that mature TCs are capable of interfering with BC regeneration post-HCT. Hence, our HCT combinations using WT and muMT B6 mice provide a powerful tool to study the role of TC function in the process of donor BC development post-HCT.

scholarly journals Pre-Salvage ISS and Other Important Outcome Predictors in CD34 Selected Allogeneic Hematopoietic Cell Transplant for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3473-3473
Author(s):  
Adam Bryant ◽  
Patrick Hilden ◽  
Sergio Giralt ◽  
Miguel-Angel Perales ◽  
Guenther Koehne
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Older Age ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Term Survival ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
The Impact

Abstract Introduction Despite recent therapeutic advances Multiple Myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to imid or proteasome inhibitor therapies are universally dismal.1 Allogeneic hematopoietic cell transplant (alloHCT) remains the only curative MM treatment but has been associated with historically high rates of GVHD and of non-relapse mortality (NRM), exceeding 40% in some series.2 Although these rates have decreased in recent years, the potential morbidity and mortality associated with alloHCT and the increasing availability of alternative non-transplant therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on clinical outcomes in a large cohort of relapsed/refractory (RR) MM patients who underwent CD34+ selected alloHCT at our institution. Methods This retrospective study included all MM patients who had CD34+ selected alloHCT from Jun 2010 to Dec 2015. Patients were conditioned with targeted dose busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 x 2) and fludarabine (25mg/m2 x 5) followed by infusion of a CD34+ selected peripheral blood stem cell graft, without post alloHCT GVHD prophylaxis. Estimates were given using the Kaplan-Meier and cumulative incidence methods. Competing risks for relapse, NRM, and GVHD were death, relapse, and relapse or death respectively. The log-rank and Gray's test were used to assess univariable associations. GVHD by 6 months was assessed via a landmark analysis. Results Our 73 patient cohort had a median age of 55 (37-66) and was mostly male (74%). Most patients had low risk MM by ISS (50/66, 76%) and intermediate risk MM by R-ISS (45/66, 68%) at pre-salvage assessment. Patients had a median of 4 (2-9) pre-alloHCT lines of therapy and were evenly split between patients in PR and in VGPR or CR at time of alloHCT (50% and 49%). Median HCT-CI score was 2 (range 0-6) with the majority of patients graded as intermediate or high risk (score ≥1; 55/73, 75%). At a median follow-up in survivors of 35 months (12-84) OS and PFS rates were 70% and 53% at 1 year (95% CI 58-79, 41-64) and 50% and 30% at 3 years, respectively (38-62, 19-41). The cumulative incidences of relapse were 25% and 47% at 1 and 3 years, respectively (16-35, 35-58), and 1 year NRM was 22% (13-32). Deaths were balanced between relapse and non-relapse causes (54% and 46% respectively). Incidence of grade II-IV acute GVHD was 7% at 100 days (3-14), and of chronic GVHD was 8% at 1 year (3-16). In univariable analysis, intermediate-high risk ISS assessed prior pre-alloHCT salvage therapy was associated with lower OS (3 year 30 v 54%, p=0.037), lower PFS (3 year 9 v 33%, p=0.013), and greater relapse incidence (3 year 72 v 39%, p=0.004). Older age and GVHD prior to 6 months were also associated with lower OS; older age, more heavily pre-treated disease, and worse disease status at alloHCT were associated with lower PFS; and heavier pre-alloHCT treatment was also associated with higher relapse (Table 1). Higher HCTCI was not associated with increased NRM (1 year 22 v 16 v 27% for HCTCT 0, 1-2, ≥3 respectively; p = 0.863). Discussion We describe a cohort of high-risk heavily pretreated RRMM patients with durable OS (50% at 3 years), comparatively low PFS (30% at 3 years), and historically improved rates of NRM (22% at 1 year). We also importantly identified numerous pre-alloHCT variables that were associated with survival, PFS, and relapse. Amongst these, poor ISS measured prior to pre-alloHCT salvage was consistently associated with worse survival and relapse outcomes and may speak to this score's utility as a dynamic measure of disease risk in patients exposed to multiple lines and therapy. Conclusions Our report reinforces that CD34+ selected alloHCT can achieve prolonged disease control and long term survival in high risk, heavily treated refractory MM populations, and newly describes certain pre-transplant variables that may help identify patients with better potential survival and relapse outcomes. Given the dismal prognosis and lack of established alternate therapies for RRMM patients, we advocate that identification of favorable or adverse pre-transplant variables during pre-alloHCT assessment be used to inform alloHCT decision-making rather than to exclude certain patient cohorts from this potentially effective and curative treatment option. Disclosures Perales: Abbvie: Other: Personal fees; Merck: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Takeda: Other: Personal fees; Novartis: Other: Personal fees.

scholarly journals Comparison of the Impact of Pre-Transplant Co-Morbidity Scores on Allogeneic Hematopoietic Stem Cell Transplant Outcomes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4670-4670
Author(s):  
Mohammed A. Marei ◽  
Eshetu G Atenafu ◽  
Arjun Law ◽  
Wilson Lam ◽  
Rajat Kumar ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
C Statistic ◽  
Co Morbidity ◽  
The Impact

Abstract Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for the treatment of various hematological diseases, in part due to the effect of conditioning chemotherapy, and in part due to graft-versus-malignancy effect. However, alloHCT is associated with significant morbidity and mortality. Multiple co-morbidity indices have been published in the literature for the purpose of pre-transplant risk assessment. The purpose of the presented study is to assess a number of these pre-transplant scores on a single-center transplant population and to determine the score with improved risk stratification ability using concordance statistics. Methods: We investigated the impact of the prospectively collected Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) on post-transplant outcomes for 243 recipients of allo-HCT performed between August 2014 and October 2016 at the Princess Margaret Cancer Center (Toronto, Canada), and compared this score to other pre-transplant scores including the age-adjusted HCT-CI, PAM score (Pre-transplant Assessment of Mortality Score) and the Disease Risk Index (DRI). Partitioning of the HCT-CI, HCT-CI/age and PAM scores into three groups was performed based on maximum significant differences on univariate analysis for overall survival (OS). Concordance statistics were used to compare the stratification power of the scores. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Inc, Cary, NC). Results: The median age at transplant is 56 years, patients were transplanted for AML (53%), ALL (7.5%), MDS (13.5%), MPN (14%), NHL/CLL (8.5%) and (3.5%) AA. Donors were matched related in 37%, unrelated in 59% and haploidentical in 3% of the patients. Reduced intensity conditioning chemotherapy was used in 132 patients (54%), 153 patients (63%) received in-vivo T-cell depletion by using Campath or ATG, both donor and recipient were CMV negative in 48 (20%) of the patients. DRI was high in 67 (29%), intermediate in 145 (62%) and low in 22 (9%) of patients. HCT-CI was 0 in 90 (37%), 1 in 49(21%) and ≥2 in 103 (43%) of patients. HCT-CI/age was 0 in 22 (10%), 1 in 72 (30%) and ≥2 in 148 (62%). PAM score was 1-17 in 157(68%), 18-24 in 70 (30%) and 25-27 in 7 (3%) of patients. Median follow up of survivors was 28 months (range 17-44 months). OS of the entire cohort was 51% and 43% at 2 and 5 years post-transplant respectively. Cumulative incidence of relapse (CIR) was 19% at 2 years. For OS, as grouped above, the DRI did not demonstrate a significant difference between groups (p=0.77). For HCT-CI, p=0.034 (Figure 1), for HCT-CI/age p=0.02 and for the PAM score p=0.38. For OS, for the DRI, the C-statistic was 0.51 (se=0.03, 95%CI 0.45-0.57). For the PAM score, C-statistic was 0.51 (se=0.02,95%CI 0.45-0.56). For the HCT-CI age, C-statistic was 0.56 (se=0.024, 95%CI 0.51-0.61). For the HCT-CI, C-statistic was 0.56 (se 0.02, 95% CI 0.50-0.61). For CIR, the PAM score demonstrated a superior C-statistic of 0.56 (se=0.06, 95%CI 0.44-0.67) compared to the other scores. For NRM, the HCT-CI score (Figure 2, p=0.039) is superior with C-statistic 0.56 (se=0.04, 95%CI=0.49-0.63). Conclusion: Based on the above described analysis, the original HCT-CI score as described by Sorror et aldemonstrates superior prognostic stratification ability for OS and NRM in our patient cohort compared to other scores. Further investigation for the development of an optimal risk scoring system for allogeneic HCT is required. Figure 1. Figure 1. Disclosures Kim: Paladin: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Lipton:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

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