Higher Incidence of Hemorrhagic Cystitis Following Haploidentical Related Donor Transplantation Compared with Matched Related Donor Transplantation

Copelan, Olivia; Sanikommu, Srinivasa Reddy; Trivedi, Jigar; Butler, Candace; Ai, Jing; Ragon, Brittany Knick; Jacobs, Ryan; Knight, Thomas; Usmani, Saad Z.; Grunwald, Michael R.; Ghosh, Nilanjan; Symanowski, James T.; Shahid, Zainab; Clark, Peter E.; He, Juntao

doi:10.1016/j.bbmt.2018.12.142

Cited by 46 publications

(46 citation statements)

References 26 publications

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“…Regarding viral infections, their incidence was high in early post-engraftment phase and more frequent in haploSCT recipients. Both CMV-I and viral HC were especially high in haploSCT recipients between days +30 to +90 post transplant, with incidences of 45% and 27%, respectively, comparable to other haploSCT studies [ 32 , 40 , 53 , 54 ]. Beyond day +100 rates of CMV and HC infection were similar between the different stem cell donor groups.…”

Section: Discussionsupporting

confidence: 83%

Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

García‐Cadenas

Esquirol

Bosch‐Vilaseca

et al. 2020

Bone Marrow Transplant

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Post-transplant cyclophosphamide (PTCy) has become a promising option after allo-SCT, but infections may be more common than in traditional protocols. We herein report 117 consecutive adults who received PTCy-based alloSCT in our hospital: HaploSCT (34%), MRD (19%), and VUD (47%), respectively. The 18-month incidence of severe bacterial, viral, and IFI was 56%, 69%, and 8.7%, without differences between donor type, except for CMV infection and viral hemorrhagic cystitis, which had a higher incidence in the haploSCT cohort (58% vs. 43% and 30% vs. 8% on day +90, p < 0.05). Late infections by conventional respiratory viruses were common in all groups [33/87 (38%)]. The 2-year survival was 72% and did not differ by donor type. IRM at day 30, day 100, and 18 months was 1.7%, 4.4%, and 12%, without differences by donor type (p = 0.7). The primary cause of IRM was bacterial infection (42%). Grade 2-4 acute GvHD was the only independent predictor of IRM. Donor type had no impact on IRM or on survival. In our study, severe infections were common in all donor types using PTCy, with higher rates of early post-engraftment CMV-I and viral HC in haploSCT recipients, although lethal infections were uncommon and similar in all donor types.

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Section: Discussionsupporting

confidence: 83%

Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

García‐Cadenas

Esquirol

Bosch‐Vilaseca

et al. 2020

Bone Marrow Transplant

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“…The high rates of BK-associated hemorrhagic cystitis are thought to be related to the combination of (1) a high-risk patient population with frequent BK virus detection pre-BMT conferring higher risk of symptomatic cystitis post-BMT, (2) the use of PTCy, and (3) the use of busulfan [53], with busulfan believed to be a significant cofactor given that we have not observed BK-associated hemorrhagic cystitis in our patients with PID who receive a lower-intensity transplant approach that is identical except that it does not contain busulfan. Of note, BK-associated hemorrhagic cystitis incidence did not vary with donor type, as has been shown elsewhere [54].…”

Section: Discussionsupporting

confidence: 80%

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

Dimitrova

Gea‐Banacloche

Steinberg

et al. 2020

Biology of Blood and Marrow Transplantation

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Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.

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“…11,[28][29][30] PTCY induces bidirectional tolerance, thereby allowing use of various preparative regimens with consistently low rates of TRM and GVHD yet infections and relapse remain problematic. [31][32][33][34] Early attempts to limit GVHD in haploHCT recipients utilizing ex vivo T-cell depletion were generally successful, but recipients were plagued by delayed donor T-cell reconstitution and high rates of dangerous viral infections and disease recurrence. 35,36 Subsequent strategies combating delayed reconstitution in T-cell depleted haploHCT included adoptive transfer of conventional and regulatory or genetically modified T cells.…”

Section: Discussionmentioning

confidence: 99%

Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

Mamcarz

Madden

Qudeimat

et al. 2019

Bone Marrow Transplant

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T-cell depletion of an HLA-haploidentical (haplo) graft is often used to reduce the risk of graftversus-host disease (GVHD), but the lack of donor T cells in the infused product may lead to graft failure, slow T-cell reconstitution, infections, and relapse. More selective T-cell depletion targeting CD45RA can effectively deplete naïve T cells but preserve large numbers of memory T cells leading to robust engraftment of diverse T-cell populations and reduction of viremia in the early post-transplant period. Herein, we report the outcome of 143 pediatric and young adult hematologic malignancy patients receiving a first allogeneic hematopoietic cell transplantation (HCT) on 6 consecutive ex vivo T-cell depleted haploHCT protocols over the past 15 years at a single institution-including the first 50 patients on an active CD45RA-depleted haploHCT study in which patients also received NK-cells and pharmacological GvHD prophylaxis post transplant. Our data demonstrated an increase in the 3-year overall survival and event-free survival in nonchemorefractory recipients receiving CD45RA-depleted grafts (78.9% and 77.7%, respectively) compared to historic T-cell depleted haploHCT cohorts (46.7% and 42.7%, respectively, p=0.004, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Higher Incidence of Hemorrhagic Cystitis Following Haploidentical Related Donor Transplantation Compared with Matched Related Donor Transplantation

Cited by 46 publications

References 26 publications

Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

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