Outcome of treosulfan‐based reduced‐toxicity conditioning regimens for <scp>HSCT</scp> in high‐risk patients with primary immune deficiencies

Haskoloğlu, Şule; Bal, Sevgi Köstel; İslamoğlu, Candan; Altun, Demet; Kendirli, Tanıl; Doğu, Figen; İkincioğulları, Aydan

doi:10.1111/petr.13266

Cited by 6 publications

(6 citation statements)

References 18 publications

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“…In a registry analysis of HCT-CI in nonmalignant diseases, HCT-CI scores 3 were associated with a significant decrease in survival [43] and, because severe combined immunodeficiency represented nearly half of PID patients in that study, the extent of comorbidities seen in older patients with PIDs requiring BMT was almost certainly underrepresented. Although reduced-toxicity, treosulfan-containing MAC regimens for PID have yielded very good outcomes, treosulfan is not available worldwide, rates of long-term toxicities such as infertility are not well defined, and SOS risk is not eliminated [44][45][46][47][48][49][50]. Additionally, underlying liver pathology may not always be identified pre-BMT, potentially making this patient population more vulnerable to SOS.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Although long-term complications and acute toxicity after transplantation are less prevalent with the RIC regimen, graft rejection is more likely (21). Reduced toxicity regimens are preferred for lower rates of acute and long-term complications (22). In a study by Kuskonmaz et al, ten patients with GS2 who underwent HSCT with myeloablative regimen and the survival rate was found as 80% (8/10) (23).…”

Section: Discussionmentioning

confidence: 99%

Hemophagocytic Lymphohistiocytosis in Children with Griscelli Syndrome Type 2 : Genetic, Laboratory findings and Treatment

Çay

Sezer

Karakulak

et al. 2023

Preprint

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“…Treosulfan, an alkylating drug with both myeloablative and immunosuppressive effects, exhibited an overall low acute toxicity in CGD transplants. If used as a single alkylator, treosulfan may be less gonadotoxic than other alkylators, however, there is no study yet available convincingly proving this assumption (92)(93)(94). Excellent myeloid DC (>95%) was documented in 80% of surviving patients.…”

Section: Hsct With Ric/rtc-regimens (Table 1)mentioning

confidence: 99%

Cellular Therapies in Chronic Granulomatous Disease

Güngör

Chiesa

2020

Front. Pediatr.

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Allogeneic hematopoietic stem cell transplantation (HSCT) has become the main curative treatment in patients with chronic granulomatous disease (CGD). CGD is caused by inherited defects of the phagolysomal NADPH-oxidase, leading to a lifelong propensity for invasive infections and granulomatous inflammation. After successful allogeneic HSCT, chronic infections and inflammation resolve and quality-of-life improves. Favorable long-term outcome after HSCT is dependent on the prevention of primary and secondary graft failure (GF), including falling myeloid donor chimerism (DC) below 10 %, and chronic graft-vs.-host-disease (cGVHD). The risk of GF and GvHD increases with the use of HLA-incompatible donors and this may outweigh the benefits of HSCT, mainly in patients with severe co-morbidities and in asymptomatic patients with residual NADPH-oxidase function. Seventeen scientific papers have reported on a total of 386 CGD-patients treated by HSCT with HLA-matched family/sibling (MFD/MSD), 9/10-/10/10-matched-unrelated volunteer (MUD) and cord blood donors. The median OS/EFS-rate of these 17 studies was 91 and 82%, respectively. The median rates of GF, cGVHD and de-novo autoimmune diseases were 14, 10, and 12%, respectively. Results after MFD/MSD and 10/10-MUD-transplants were rather similar, but outcome in adults with significant co-morbidities and after transplants with 9/10 HLA-MUD were less successful, mainly due to increased GF and chronic GVHD. Transplantation protocols using T-cell depleted haploidentical donors with post-transplant cyclophosphamide or TCR-alpha/beta depletion have recently reported promising results. Autologous gene-therapy after lentiviral transduction of HSC achieved OS/EFS-rates of 78/67%, respectively. Careful retrospective and prospective studies are mandatory to ascertain the most effective cellular therapies in patients with CGD.

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Outcome of treosulfan‐based reduced‐toxicity conditioning regimens for HSCT in high‐risk patients with primary immune deficiencies

Abstract: Treosulfan-based conditioning regimens before HSCT are associated with lower toxicity compared to myeloablative regimens, are safe, and have high engraftment rates with full-donor chimerism in patients having PID, regardless of the specified genetic diagnosis and donor type.

Cited by 6 publications

References 18 publications

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

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

Hemophagocytic Lymphohistiocytosis in Children with Griscelli Syndrome Type 2 : Genetic, Laboratory findings and Treatment

Cellular Therapies in Chronic Granulomatous Disease

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