ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia

Faulkner, Lawrence; Uderzo, C; Khalid, Sadaf; Marwah, Priya; Soni, Rajpreet; Yaqub, Naila; Amanat, Samina; Fatima, Itrat; Gilani, Sarah Khan; Zahra, Tatheer; Ramprakash, Stalin; Gooneratne, Lallindra; Dissanayake, Ruwangi; Williams, Senani; Rathnayake, Wasantha; Srinivas, R; Sedai, Amit; Ankita, Kumari; Parmar, L; Dhanya, Rakesh; Agarwal, Rajat

doi:10.1182/bloodadvances.2016004119

Cited by 22 publications

(16 citation statements)

References 57 publications

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“…Bone marrow transplantation (BMT) is considered the gold standard for treating severe β-TM. 5 When compared with BMT without ATG, the outcomes after human leukocyte antigen-matched sibling donor transplantation, the results using an ATG-containing preparative regimen in this study were similar to or better than those reported previously. 6,7 Similarly, the hematopoietic reconstruction was consistent with or even better than previously published data.…”

Section: Discussionsupporting

confidence: 82%

Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children

Qin

Shi

et al. 2019

European J of Haematology

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Background The clinical outcome of hematopoietic stem cell transplantation (HSCT) in those with severe beta‐thalassemia (β‐TM) is closely related to post‐transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce. Methods A prospective analysis of the clinical outcome and IR in 47 children with severe β‐TM who underwent in vivo T‐cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. Immune reconstitution, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measured. Results In the first year after HSCT, bacterial infections and cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4+ T‐cell recovery was observed. The B cells recovered within 6 months. Natural killer (NK) cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB + BM) group had slower T‐cell recovery, and higher B cells and NK cells in comparison with peripheral blood and bone marrow (PB + BM) group. Conclusions The high incidence of infection within 1 year after in vivo T‐cell depletion myeloablative conditioning HSCT in severe β‐TM was consistent with poor IR.

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Section: Discussionsupporting

confidence: 82%

Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children

Qin

Shi

et al. 2019

European J of Haematology

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“…Our outcome analysis seems to suggest that ST versus FT HLA typing might be associated with sizable differences in events related to HLA disparities, particularly GVHD. The unexpected finding of the slight increase in rejection rates observed in the FT cohort might be related to small sample size or to a graft-enhancing effect of HLA disparity in the GVH direction related to early antithymocyte globulin timing (days -12 to -10) [10] sparing alloreactive donor lymphocytes infused with the marrow. Although this type of analysis has major limitations given its retrospective nature, it has the advantage of being focused on a relatively homogeneous group of patients with a single disease at risk for both rejection and GVHD.…”

Section: Discussionmentioning

confidence: 89%

“…All patients underwent transplantation between August 2013 and June 2016 after conditioning with a combination of rabbit anti-thymocyte globulin, busulfan, and cyclophosphamide followed by the infusion of freshly harvested granulocyte colony-stimulating factor-primed donor marrow on day 0. Rejection/GVHD prophylaxis consisted of cyclosporin A, methotrexate, and low-dose prednisone [10].…”

Section: Methodsmentioning

confidence: 99%

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent

Agarwal

Ankita

Sedai³

et al. 2017

Biology of Blood and Marrow Transplantation

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Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22%) consanguinity was unknown. We identified 18 donors (6%; 13 siblings and 5 parents) who would have been considered a 12/12 match by LR HLA typing alone but were found not to match on extended HR typing. In this group, 11 donors (61%) were from consanguineous families, 3 donors (17%) had no reported consanguinity, and in 4 donors (22%) consanguinity was unknown. Outcome analysis showed that the actuarial proportion of patients with GVHD was 4% in the FT group compared with 16% in the ST group, with log-rank P = .1952. The ST group included 2 patients with grade III-IV acute GVHD and 1 patient each with moderate and severe chronic GVHD, whereas the FT group only 1 patient with grade III acute GVHD. We conclude that even in the context of related donors, the use of LR and/or 3-loci (A, B, and DRB1) HR HLA typing might result in a sizable risk of missing a clinically relevant mismatch, which may have an adverse impact on transplantation outcomes. In the Indian subcontinent, this observation is not limited to putatively compatible parents or consanguineous ...

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“…Identification of candidates suitable for transplantation led to 391 patients getting human leukocyte antigen-typed and prepared for bone marrow transplantation from these centers. In all, 43 were transplanted with overall survival of 93% and disease-free survival of 77% at a mean cost of US $13,000 per transplant, including pretransplant preparation and late complications [45,46]. For these patients, online software specific for bone marrow transplantation was used [47].…”

Section: Resultsmentioning

confidence: 99%

Information Technology–Assisted Treatment Planning and Performance Assessment for Severe Thalassemia Care in Low- and Middle-Income Countries: Observational Study

Agarwal¹,

Sedai²,

Ankita³

et al. 2019

JMIR Med Inform

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Background Successful models of information and communication technology (ICT) applied to cost-effective delivery of quality care in low- and middle-income countries (LMIC) are an increasing necessity. Severe thalassemia is one of the most common life-threatening noncommunicable diseases of children globally. Objective The aim was to study the impact of ICT on quality of care for severe thalassemia patients in LMIC. Methods A total of 1110 patients with severe thalassemia from five centers in India were followed over a 1-year period. The impact of consistent use of a Web-based platform designed to assist comprehensive management of severe thalassemia (ThalCare) on key indicators of quality of care such as minimum (pretransfusion) hemoglobin, serum ferritin, liver size, and spleen size were assessed. Results Overall improvements in initial hemoglobin, ferritin, and liver and spleen size were significant ( P <.001 for each). For four centers, the improvement in mean pretransfusion hemoglobin level was statistically significant ( P <.001). Four of five centers achieved reduction in mean ferritin levels, with two displaying a significant drop in ferritin ( P =.004 and P <.001). One of the five centers did not record liver and spleen size on palpation, but of the remaining four centers, two witnessed a large drop in liver and spleen size ( P <.01), one witnessed moderate drop ( P =.05 for liver; P =.03 for spleen size), while the fourth witnessed a moderate increase in liver size ( P =.08) and insignificant change in spleen size ( P =.12). Conclusions Implementation of computer-assisted treatment planning and performance assessment consistently and positively impacted indexes reflecting effective delivery of care to patients suffering from severe thalassemia in LMIC.

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ATG vs thiotepa with busulfan and cyclophosphamide in matched-related bone marrow transplantation for thalassemia

Cited by 22 publications

References 57 publications

Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children

Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent

Information Technology–Assisted Treatment Planning and Performance Assessment for Severe Thalassemia Care in Low- and Middle-Income Countries: Observational Study

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