Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 914-916

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-164600

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Transplantation, Wiley, Vol. 21, No. 3 ( 2007-05), p. 295-300

Abstract: Abstract:  Background:  In the multicenter, open‐label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA‐ME, day 0) or delayed CsA‐ME (day 6) with enteric‐coated mycophenolate sodium (EC‐MPS), steroids and interleukin‐2 receptor induction. One‐yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post‐transplant. Methods:  All patients completing the one‐yr core study on‐treatment were eligible to enter the extension study. Results:  Of the 203 patients, 153 completed the core trial on‐treatment; 144 (94%) entered the extension study with a minimum follow‐up of one yr (73 early CsA‐ME, 71 delayed CsA‐ME). In 75% of patients receiving EC‐MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post‐transplant and was similar in the early and delayed CsA‐ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA‐ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. Conclusion:  These results suggest that a regimen of CsA‐ME, EC‐MPS and steroids results in excellent survival rates with stable renal function over a mean follow‐up of 30 months. Immediate introduction of CsA‐ME has no deleterious effect on long‐term renal function, even among patients with delayed graft function.

Type of Medium: Online Resource

ISSN: 0902-0063 , 1399-0012

URL: Issue

URL: Article

DOI: 10.1111/ctr.2007.21.issue-3

DOI: 10.1111/j.1399-0012.2007.00660.x

Language: English

Publisher: Wiley

Publication Date: 2007

detail.hit.zdb_id: 2739458-X

detail.hit.zdb_id: 2004801-4

In: Transplant Infectious Disease, Wiley, Vol. 23, No. 1 ( 2021-02)

Abstract: Reactivation of human herpesvirus 6 (HHV‐6) occurs in 30%‐50% of patients (pts) who receive allogeneic (allo) hematopoietic stem cell transplant (HCT). However, the recommendation for post‐transplant HHV‐6 monitoring and treatment in pediatric pts is not well established. Methods HHV‐6 incidence rates and the clinical outcomes were reported for 139 pediatric pts (≤18 years) undergoing first allo‐HCT at City of Hope from July 2011 to July 2017, for whom HHV‐6 was monitored weekly throughout HCT hospitalization. For 57 pediatric pts, who underwent first HCT from January 2009 to July 2011, HHV‐6 was tested as clinically indicated and only rates of HHV‐6 viremia were collected. Results From July 2011 to July 2017, HHV‐6 was detected in 88/139 pts (63%). The frequency of HHV‐6 viremia was associated with malignant diagnoses, myeloablative conditioning, and cord blood HCT. Treatment with antiviral agents was offered to symptomatic pts with a higher viral load (VL), for whom the time to VL clearance was longer and the frequency of subsequent recurrences was higher. Pts with a lower VL cleared HHV‐6 without treatment. HHV‐6 viremia was associated with a higher frequency of grade II‐IV acute graft‐versus‐host disease (GVHD) ( P  = .022), but did not affect overall survival (OS), disease‐free survival (DFS), non‐relapsed mortality (NRM), myeloid, or platelet (Plt) engraftment. Conclusions HHV‐6 weekly screening is not necessary for all HCT pts but may be considered for high‐risk pts with malignant diagnoses undergoing cord blood HCT; otherwise, HHV‐6 should be tested as clinically indicated. Only symptomatic pts (especially with a high VL  〉  25 000) could benefit from treatment. HHV‐6 viremia at the time of initiation and administration of the conditioning regimen cleared promptly without the need to augment the transplant process.

Type of Medium: Online Resource

ISSN: 1398-2273 , 1399-3062

URL: Issue

URL: Article

DOI: 10.1111/tid.v23.1

DOI: 10.1111/tid.13453

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2010983-0

In: Blood Advances, American Society of Hematology, Vol. 7, No. 12 ( 2023-06-27), p. 2758-2771

Abstract: Chimeric antigen receptor–associated hemophagocytic lymphohistiocytosis (HLH)–like toxicities (LTs) involving hyperferritinemia, multiorgan dysfunction, coagulopathy, and/or hemophagocytosis are described as occurring in a subset of patients with cytokine release syndrome (CRS). Case series report poor outcomes for those with B-cell acute lymphoblastic leukemia (B-ALL) who develop HLH-LTs, although larger outcomes analyses of children and young adults (CAYAs) with B-ALL who develop these toxicities after the administration of commercially available tisagenlecleucel are not described. Using a multi-institutional database of 185 CAYAs with B-ALL, we conducted a retrospective cohort study including groups that developed HLH-LTs, high-grade (HG) CRS without HLH-LTs, or no to low-grade (NLG) CRS without HLH-LTs. Primary objectives included characterizing the incidence, outcomes, and preinfusion factors associated with HLH-LTs. Among 185 CAYAs infused with tisagenlecleucel, 26 (14.1%) met the criteria for HLH-LTs. One-year overall survival and relapse-free survival were 25.7% and 4.7%, respectively, in those with HLH-LTs compared with 80.1% and 57.6%, respectively, in those without. In multivariable analysis for death, meeting criteria for HLH-LTs carried a hazard ratio of 4.61 (95% confidence interval, 2.41-8.83), controlling for disease burden, age, and sex. Patients who developed HLH-LTs had higher pretisagenlecleucel disease burden, ferritin, and C-reactive protein levels and lower platelet and absolute neutrophil counts than patients with HG- or NLG-CRS without HLH-LTs. Overall, CAYAs with B-ALL who developed HLH-LTs after tisagenlecleucel experienced high rates of relapse and nonrelapse mortality, indicating the urgent need for further investigations into prevention and optimal management of patients who develop HLH-LTs after tisagenlecleucel.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2022008893

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 2876449-3

In: Neurosurgical Focus, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 42, No. 6 ( 2017-05), p. E8-

Abstract: The utilization of the Pipeline embolization device (PED) has increased significantly since its inception and original approval for use in large, broad-necked aneurysms of the internal carotid artery. While microsurgical clipping and advances in endovascular techniques have improved overall efficacy in achieving complete occlusion, recurrences still occur, and the best modality for retreatment remains controversial. Despite its efficacy in this setting, the role of PED utilization in the setting of recurrent aneurysms has not yet been well defined. This study was designed to assess the safety and efficacy of PED in the recurrence of previously treated aneurysms. METHODS The authors reviewed a total of 13 cases in which patients underwent secondary placement of a PED for aneurysm recurrence following prior treatment with another modality. The PEDs were used to treat aneurysm recurrence or residual following endovascular coiling in 7 cases, flow diversion in 2, and microsurgical clipping in 4. The mean time between initial treatment and retreatment with a PED was 28.1 months, 12 months, and 88.7 months, respectively. Clinical outcomes, including complications and modified Rankin Scale (mRS) scores, and angiographic evidence of complete occlusion were tabulated for each treatment group. RESULTS All PEDs were successfully placed without periprocedural complications. The rate of complete occlusion was 80% at 6 months after PED placement and 100% at 12 months in these patients who underwent PED placement following failed endovascular coiling; there were no adverse clinical sequelae at a mean follow-up of 26.1 months. In the 2 cases in which PEDs were placed for treatment of residual aneurysms following prior flow diversion, 1 patient demonstrated asymptomatic vessel occlusion at 6 months, and the other exhibited complete aneurysm occlusion at 12 months. In patients with aneurysm recurrence following prior microsurgical clipping, the rate of complete occlusion was 100% at 6 and 12 months, with no adverse sequelae noted at a mean clinical follow-up of 27.7 months. CONCLUSIONS The treatment of recurrent aneurysms with the PED following previous endovascular coiling, flow diversion, or microsurgical clipping is associated with a high rate of complete occlusion and minimal morbidity.

Type of Medium: Online Resource

ISSN: 1092-0684

URL: Article

DOI: 10.3171/2017.3.FOCUS1744

Language: Unknown

Publisher: Journal of Neurosurgery Publishing Group (JNSPG)

Publication Date: 2017

detail.hit.zdb_id: 2026589-X

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 14-15

Abstract: Introduction: Chimeric Antigen Receptor (CAR) T cell therapy targeting CD19 has shifted our treatment approach for relapsed and refractory (r/r) pediatric B cell acute lymphoblastic leukemia (ALL). The landmark ELIANA pediatric trial studying tisagenlecleucel, CD19-specific CAR T cells, demonstrated a complete response (CR) rate of 81% in 75 infused patients and 12 month overall survival (OS) and event-free survival (EFS) rates of 76% and 50% respectively. Cytokine release syndrome (CRS) and neurotoxicity rates of 77% and 40% were respectively reported. In August 2017, the FDA approved tisagenlecleucel for B-cell ALL that is refractory or in second or greater relapse in patients up to age 25. With CAR commercialization, institutions deliver tisagenlecleucel without the regulation of a clinical study and practices relating to CAR delivery and reporting remain heterogeneous. Here, we report real world clinical outcomes using commercially available tisagenlecleucel for pediatric r/r B-ALL. Methods and Results: Retrospective data were collected from PRWCC member institutions (n=15) and included 200 patients. This includes 15 (7.5%) patients not infused due to manufacturing failure (n=6), death from disease progression and/or toxicity (n=7), or physician discretion following disease remission from prior therapy(n=2). The remaining 185 patients (92.5%) were infused with tisagenlecleucel, including 87% (161) receiving standard-of-care CAR T cell products meeting manufacturing release criteria and 13% (24) receiving CD19-CAR T cells manufactured by Novartis and provided on the managed access program (NCT03601442; n=14) or with single-patient IND approval (n=10). At time of CAR T cell infusion, median age was 12 years (range 0-26) with 40% females and 60% males. Median duration of follow-up at time of analysis was 11.2 months (range 0.2-28.8). The CR rate at 1 month follow up was 79% (156/198) on an intent-to-treat basis and 85% (156/184) among evaluable infused patients. Of infused patients achieving morphologic CR with available testing, 97% (148/153) were negative for MRD by flow cytometry. Duration of remission at 6 and 12 months among patients who achieved CR was 75% and 63% respectively, with 35% (55/156) of responders experiencing relapse. At time of relapse, 41% (21/51) of evaluable patients had relapse with CD19- disease and 59% (30/51) had continued CD19 expression. OS and EFS rates were 85% and 64% at 6 months and 72% and 51% at 12 months, respectively. CRS and neurotoxicity of any grade were seen in 60% (111/184) and 22% (39/181) of evaluable patients with ≥ grade 3 CRS and neurotoxicity rates of 19% (35/184) and 7% (12/181) respectively. One grade 5 CRS and 1 grade 5 neurotoxicity (intracranial hemorrhage) were reported. Post infusion toxicity management included tocilizumab in 26% (47/184) and systemic steroids in 14% (25/184) of patients. Among 181 infused patients with documented disease burden, 51% (95) had high burden (HB) disease , as defined by & gt;5% bone marrow lymphoblasts, peripheral blood lymphoblasts, CNS3 status or non-CNS extramedullary (EM) site of disease; 22% (40) had low burden (LB) disease, defined by detectable disease not meeting the HB criteria; and 25% (46) had no detectable disease (NDD) at time of last evaluation prior to CAR infusion. The morphologic CR rate was lower at day 28 in HB vs. LB and NDD (74% vs. 98% and 96%) and the OS and EFS were lower among patients with HB at 6 mo [OS; 75% (HB), 94%(LB), 98% (NDD), EFS; 50% (HB), 86% (LB), 75%(NDD), p & lt;0.0001] and 12 mo [OS; 58% (HB), 85% (LB), 95% (NDD), EFS; 34% (HB), 69%(LB), 72%(NDD), p & lt;0.0001]. Multivariate analysis will be presented at the meeting. Conclusions: This retrospective, multi-institutional analysis describes real world outcomes using tisagenlecleucel to treat pediatric r/r B-ALL. Early responses at 1 month and OS and EFS at 6 and 12 months are comparable to reported ELIANA trial outcomes. Safety is demonstrated in this cohort with lower rates or CRS and neurotoxicity, likely related to a lower disease burden cohort. Continued relapse and decrease in OS without evident plateau is seen following 6 months post-infusion warranting expanded follow up. Comparative analysis of outcomes in patient cohorts with varying disease burden demonstrate decreased CR, EFS and OS in patients with high disease burden as compared to patients with lower disease burden or no detectable disease at last evaluation prior to CAR infusion. Disclosures Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees. Stefanski:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Margossian:Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Verneris:Fate Therapeutics: Consultancy, Current equity holder in publicly-traded company; Novartis: Membership on an entity's Board of Directors or advisory committees; Bmogen: Consultancy, Current equity holder in publicly-traded company; Uptodate: Consultancy. Myers:Novartis: Consultancy, Honoraria, Other: ELIANA trial Steering Committee, Speakers Bureau. Brown:Jazz: Honoraria; Servier: Honoraria; Janssen: Consultancy; Novartis: Consultancy. Qayed:Novartis: Consultancy; Mesoblast: Consultancy. Hermiston:Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Satwani:Takeda: Consultancy; Mesoblast: Consultancy. Curran:Novartis: Consultancy, Research Funding; Mesoblast: Consultancy; Celgene: Research Funding. Mackall:Lyell Immunopharma: Consultancy, Current equity holder in private company; Nektar Therapeutics: Consultancy; NeoImmune Tech: Consultancy; Apricity Health: Consultancy, Current equity holder in private company; BMS: Consultancy; Allogene: Current equity holder in publicly-traded company. Laetsch:Cellectis: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; Bayer: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-134472

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 10-11

Abstract: Background: Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatment regimens. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been used as a consolidation strategy in remission states (CR1 or above) endorsed by the NCCN guidelines in appropriate patients. 5-year DFS is reported at 70% for alk -ve anaplastic large cell lymphoma (ALCL) and 30-40% for most other histologies (D'Amore et al, 2012, JCO). It is also performed in the relapsed settings if no previous ASCT performed and allogeneic transplant is not an option. CD25 is a targetable protein expressed differentially in PTCL and antibody based anti-CD25 therapies are efficacious in PTCL i.e denileukin diftitox (Foss et al Blood 2006, Dang et al, BJH 2006) , monoclonal antibody dacluzimab (Waldman et al 1995 Blood). Yttrium-90 (90Y) labeled chimeric antiCD25 antibody basiliximab emits beta particles and has been shown to inhibit the growth of human ALCL tumors and increase survival in SUDHL-1 xenograft mice (Zhang et al 2009 Cancer Biother Radiopharm). Previous investigations at COH by Raubitschek, Colcher et al established a safe does of Yttrium-90 (90Y) labeled basiliximab at 0.4mCi/kg in combination with BEAM. This is a phase 1 clinical trial of a novel conditioning regimen that includes the use of Yttrium-90 (90Y) labeled basiliximab with BEAM chemotherapy for PTCL patients eligible for ASCT. The trial utilizes a modified version of the rolling 6 design (Skolnik et al) to test 3 dose levels of Yttrium-90 (90Y) Basiliximab i.e 0.4mCi/kg, 0.5miC/kg and 0.6mCi/kg with the primary objective of evaluating the safety and tolerability of this combination and to establish the MTD. Secondary objectives include estimating incidence of relapse, OS, PFS, NRM at day 100, 1 year and 2 years post-transplant. Patients and Methods: Dose limiting toxicity (DLT) is defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. The study/treatment schema is shown in Figure 1. Results: From 07/29/2015 to 06/10/2020, 20 patients underwent ASCT on this trial; n=4 at 0.4mCi/kg n=4 at 0.5mCi/kg and n=12 at 0.6mCi/kg. Median age at ASCT was 51 years (range: 18-76), and histologies included; PTCL-nos (n=10); alk-ve ALCL (n=5); angioimmunoblastic T-cell lymphoma (n=3); and intestinal T-cell lymphoma (n=2). Disease status at ASCT were CR1 in18, CR2 in 2 patients. Median number of prior therapies was 1 (range: 1-4). At a median follow-up of 17.1 months (range: 0.9-26.2), 12 patients remain in remission, 8 have relapsed out of which 5 have died of progressive lymphoma. OS was 100% (95% CI: N/A) at 100-days, and 83% (95% CI: 57-94) at 1 year. Non-relapse Mortality was 0% at both 100-days and 1-year. All patients successfully engrafted with the median days to ANC & gt;= 500/ul was 10 (range: 10 - 21), and days to PLT & gt;= 20,000/ul: 13 (12 - 92). Overall, no dose limiting toxicities were experienced. The most common/highest grade toxicity experienced (per Bearman Scale) was grade 2 stomatitis, which was seen in 3 patients at 0.4mCi/kg; 4 patients at 0.5 mCi/kg, and 7 at0.6mCi/kg. The only other toxicities seen were grade 2 GI in 2 patients at 0.4mCi/kg, and grade 2 bladder in one patient at 0.6mCi/kg dose.. Toxicities & gt;grade 2 were not seen. Conclusion: aTac- BEAM appears to be safe as an ASCT conditioning regimen for PTCL with no increased toxicity as compared to the historical toxicities seen with BEAM alone in this patient population (D'Amore 2012 J of Clin Onc). The dose level 0.6mCi/kg will likely be the recommended phase II dose. An expanded phase is planned to evaluate the efficacy of this regimen followed by a randomized trial of BEAM alone plus a combination of aTac- BEAM. Figure 1 Disclosures Zain: Mundi Pharma: Research Funding; Seattle Genetics: Research Funding; Kyowa Kirin: Research Funding. Herrera:Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Merck: Consultancy, Research Funding. Salhotra:Kadmon: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Nakamura:NapaJen Pharma: Consultancy; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Merck: Other: advisory board meeting; Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Kadmon Corporation: Other: Advisory board meeting. OffLabel Disclosure: Yittrium labelled Basiliximab

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-141114

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 49-50

Abstract: Mismatched unrelated donors (MMUD) has improved access to hematopoietic cell transplantation (HCT) for underrepresented minority groups. However, MMUD HCT is historically associated with inferior outcomes primarily due to the increased risk of graft-versus-host disease (GvHD), when conventional calcineurin inhibitor-based GvHD prophylaxis is used. Post-transplant cyclophosphamide (PTCy) is an established and effective agent as part of GvHD prophylaxis post haploidentical HCT, which has been increasingly used in the matched donor HCT setting. To date, there have been no prospective studies reporting the efficacy of PTCy after peripheral blood stem cell (PBSC) MMUD HCT. Here, we conducted a pilot trial to estimate the GVHD-free relapse/progression-free survival (GRFS) at one-year post HCT and to evaluate the efficacy of PTCy as GvHD prophylaxis using either an ablative or reduced intensity conditioning regimen after PBSC MMUD HCT (NCT 03128359). Patients with hematologic malignancies (n=38), who were ≤75 years old, had KPS of ≥70%, and were scheduled for HCT from a 7/8 HLA-matched (A-, B-, C-, and DR-) donor were eligible. Patients received myeloablative conditioning (MAC, n=19) using Fludarabine (90 mg/m2) and FTBI (1200 cGy), or reduced intensity conditioning (RIC, n=19) using Fludarabine (100 mg/m2) and Melphalan (140 mg/m2 or 100 mg/m2 if & gt;60 years old). All patients received GCSF-mobilized PBSC as the graft source. GvHD prophylaxis consisted of PTCy (50mg/kg x2 days), Tacrolimus (1mg/d), and MMF (1g x3/d). Overall, patients' median age at HCT was 53 years (range: 21-72), and 50% were male. HCT indication was AML (n=17), ALL (n=8), MDS (n=6), CML (n=3), NHL (n=3), or CLL (n=1). DRI was low in 18 (47%), intermediate in 14 (37%) and high/very high in 6 (16%) patients. At HCT, 29 patients were in complete remission and 9 had active disease (Median BM blast: 3.4, range: 0-7). HCT-CI was & gt;2 in 17 patients (45%). Donors (median age: 32 years, range: 19-53) were mismatched at HLA-A (n=15), -B (n=12), -C (n=8), or DR-loci (n=5) with the median number of mismatches of 2 (range: 1-4) out of 12. The median CD34+ cell dose was 5.45×106/kg (range: 2.39-9.35). Median time to neutrophil engraftment was 16 days (range: 13-35). Complete donor chimerism ( & gt;99% if PCR or 95% if STR) was achieved in 36 patients (95%) by day 30 ± 7 days. With a median follow-up period of 18.1 months (range: 4.6 - 25.0), 1-year overall survival (OS) and GRFS were 87% (95% CI: 71-94) and 68% (95% CI: 51-81), respectively (Figure). Non-relapse mortality and relapse rate at 1 year were 11% (95% CI:4-27) and 11% (95% CI: 4-27), respectively (Figure). Cumulative incidence of day 100 acute GvHD grade 2-4 and 3-4 were 51% (95% CI: 38-70) and 19% (95% CI: 10-37), respectively. By NIH criteria, 1-year chronic GvHD was 52% (95% CI: 37-72) with moderate/severe chronic GvHD in 3% (95% CI 0.4-19). By exploratory post-hoc univariable analysis, RIC (vs. MAC) and intermediate/high-risk DRI (vs. low risk) were associated with worse GRFS (HR=4.7, 95%CI: 1.3-16.8, p=0.01 and HR=3.8, 95%CI: 1.1-13.8, p=0.04, respectively). The class and number of HLA mismatch, CD34+ cell dose, and absolute lymphocyte count were not predictive of GRFS. Infectious complications from Day -9 to +100 included CMV viremia (n=16) respiratory infections (n=5, 2 patients with lower respiratory), and BK virus cystitis (n=5). Fifteen patients had bacteremia (6 with GNR) and 4 had C. difficile colitis. Correlative flow-cytometry data was available for 29 patients. T cells reconstitution ( & gt;300/ul) was seen in 17 patients (59%) by day 100 (n=11) or day 180 (n=6). NK cell recovery ( & gt;150/ul) was seen in 24 patients (85.7%) by day 28 (n=9), day 100 (n=11), or day 180 (n=4). NK cells were predominantly highly cytotoxic CD3-CD56dim. Regulatory T cell counts on day 30 was associated with GRFS: median: 0.20/ul (range: 0.04-2.21) in the group with GRFS event (n=8) compared with 0.68/ul (range: 0.08-23.0, p=0.03) in the group with no GRFS event (n=19). Our pilot trial showed highly promising OS/GRFS in patients receiving PBSC MMUD HCT, indicating that PTCy is an effective GvHD prophylaxis platform in this setting. Our data support further development of PTCy in MMUD HCT to improve the access to and outcome of HCT in patients with hematologic disorders who have otherwise no suitable donor. Figure Disclosures Al Malki: Neximmune: Consultancy; Rigel Pharma: Consultancy; Jazz Pharmacuticals, Inc: Consultancy. Ali:Incyte Corporation: Consultancy. Stein:Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci:Merck: Other: Research Support (Investigation Initiated Clinical Trial); Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Abbvie: Speakers Bureau; Iaso Bio: Membership on an entity's Board of Directors or advisory committees. Nakamura:Merck: Other: advisory board meeting; NapaJen Pharma: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-142807

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 21-22

Abstract: The use of post-transplant cyclophosphamide (PTCy) as graft-versus-host-disease (GvHD) prophylaxis after hematopoietic cell transplantation (HCT) has increased significantly over the past decade due to expansion of donor pool with haploidentical and mismatched unrelated donors. A recently completed phase 2 study, PROGRESS-2 (NCT02345850), has highlighted the efficacy of PTCy in the matched donor setting. Hemorrhagic cystitis (HC) is the most notable toxicity associated with high dose Cy. However, data specific to the incidence and severity of HC in the post HCT setting is sparse, with no consensus on best practices to prevent HC in patients receiving PTCy. Current strategies to prevent HC in PTCy setting have been adapted from data in pre-HCT Cy (conditioning setting), such as hyperhydration with forced diuresis, continuous bladder irrigation, mesna as an intermittent and continuous infusion, or a combination of these methods. The aim of our study was to describe the incidence and severity of HC in patients undergoing HCT with PTCy as GvHD prophylaxis, identifying potential risk factors and impact of HC on HCT outcomes. We retrospectively reviewed 194 consecutive patients who underwent their first HCT with PTCy from 2014 to 2018 at our center. More than half of the patients (53%) received myeloablative conditioning regimen with majority receiving peripheral blood stem cells (81%) from haploidentical donors (96%). GvHD prophylaxis was unified with PTCy (50 mg/kg on Days +3 and +4), in addition to MMF (1 gm 3x daily starting on Day +5) and tacrolimus (1 mg as a continuous infusion daily starting on Day +5). Standard HC prophylaxis was hyperhydration with forced diuresis and mesna at 320% the daily dose of PTCy. Incidence of HC was based on physician documentation or presence of blood in urinalysis up to Day +100. To determine severity of HC, CTCAE 5.0 grading system was used. Median age of patients was 45 years (range: 2-73), with 60% of patients being male. KPS was ≥80% in 83% of patient and 40% had HCT-CI of ≥2. The most common diagnoses included: AML (41%), ALL (24%) and MDS/MPN (19%). There were 55 patients who received ≥3 lines of therapy, 116 patients received & lt;3 lines of therapy pre-HCT, and 23 patients did not receive chemotherapy before HCT. DRI was high/very high in 38% of patients. Incidence, median onset, median days until resolution, severity, and the types of intervention for treatment of HC are displayed in Table 1. At a median onset of 12 days (range: 3-71) after HCT, a total of 61 patients (31.4%) developed Grade 1-2 (88.5%) and Grade 3 (11.5%); none of the patients developed Grade 4 HC. Viral HC (presence of either BK [n=26] or adenovirus [n=0] in urine) and non-viral HC were developed at a median of 34 (range: 6-71) and 7 days (range: 3-59, p & lt;0.001), respectively. Most patients improved with supportive care over a median of 9 days (range: 1-69). Seven patients (11.5%) required continuous bladder irrigation, and six received anti-viral therapy. In multivariate analysis, age above 60 years (HR 4.16, 95% CI 1.52-11.42, p = 0.006) and myeloablative conditioning (HR 2.44, 95% CI 0.99-6.05, p = 0.054 [trend]) were associated with higher risk for HC. Disease type and risk, performance status and prior chemotherapy history were not associated with higher risk of HC in our cohort. By multivariate analysis, the incidence of HC or severe HC by Day +100 post-HCT was not associated with overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM), or grade 3-4 acute GvHD. In conclusion, hyperhydration with forced diuresis added to aggressive mesna dosing is an effective strategy in preventing severe HC in HCT patients receiving PTCy as GvHD prophylaxis. Incidence of Grade 3 or 4 HC was low and transient and did not impact HCT outcomes. Viral HC had a significantly later onset than non-viral HC, suggesting a different pathophysiology. Older age and myeloablative conditioning were independent factors for higher incidence of HC in our cohort. Disclosures Ali: Incyte Corporation: Consultancy. Salhotra:Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees. Aribi:Seattle Genetics: Consultancy. Pullarkat:Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stein:Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci:Merck: Other: Research Support (Investigation Initiated Clinical Trial); Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Research Support (Investigation Initiated Clinical Trial). Nakamura:NapaJen Pharma: Consultancy; Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Magenta Therapeutics: Other: Advisory board meeting; Celgene: Other: Support on seminar; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting. Al Malki:Rigel Pharma: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Neximmune: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-139993

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 24, No. 3 ( 2018-03), p. S384-

Type of Medium: Online Resource

ISSN: 1083-8791

URL: Article

DOI: 10.1016/j.bbmt.2017.12.474

Language: English

Publisher: Elsevier BV

Publication Date: 2018

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