Graft failure in the modern era of allogeneic hematopoietic SCT

Olsson, Richard F.; Remberger, Mats; Schaffer, Marie; Dm, Berggren; Bm, Svahn; Mattsson, Jonas; Ringdén, Olle

doi:10.1038/bmt.2012.239

Cited by 222 publications

(186 citation statements)

References 56 publications

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“…However, in this study allogeneic SCT had been performed for multiple (hematologic and non-hematologic) indications and only a small number of MF patients was included (n = 21). 26 Other indirect support for our hypothesis stems from the reports by Kröger et al They used a RIC regimen, incorporating fludarabine, busulfan and ATG, and reached the lowest graft failure rates reported to date (2-5%). 12,27 In contrast, Ballen et al Abbreviations: cy = cyclophosphamide; DIPSS = Dynamic International Prognostic Scoring System; Flu = fludarabine; JAK2 = Janus kinase 2; Mel = melphalan; MSD = matched sibling donor; NMA = non-myeloablative; PTS = predictive transplant score; RIC = reduced-intensity conditioning; SCT = stem cell transplantation; TRM = treatment-related mortality; UD = unrelated donor.…”

Section: Discussionmentioning

confidence: 72%

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Slot

Smits

Donk

et al. 2015

Bone Marrow Transplant

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In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and nonmyeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P = 0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.

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Section: Discussionmentioning

confidence: 72%

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Slot

Smits

Donk

et al. 2015

Bone Marrow Transplant

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“…Within this subgroup, 25-OH-D 3 levels were not significantly associated with other known risk factors for rejection, anti-T-cell treatment, HLA mismatch or non-malignant disease. 22 Low 25-OH-D 3 levels were more common among patients receiving cord blood transplants, but removing these patients from the analysis did not change the result.…”

Section: Vitamin D Deficiency and Complications After Hsct L Von Bahrmentioning

confidence: 88%

“…As 11 out of 13 cases of graft failure were in patients having received reduced intensity conditioning (RIC), and RIC has previously been shown to be a risk factor for graft failure, 22 we chose this subgroup for a post hoc analysis (Figure 4). Abbreviations: cGvHD = chronic GvHD; CI = confidence interval; HR = hazards ratio.…”

Section: Survival and Relapsementioning

confidence: 99%

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Bahr

Blennow

Alm

et al. 2015

Bone Marrow Transplant

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Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

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“…Some authors have reported that the overall incidence of GF after CBT is between 10% and 20% 3, 4, 5. GF can be due to immunological rejection of donor cells by residual host lymphocytes, the presence of donor‐specific anti‐HLA antibodies (DSA), or nonimmunologic mechanisms such as poor stem cell viability and viral infections 6, 7. Particularly, factors associated with GF in CBT can be inherently low stem cell doses, HLA mismatch, relative immaturity of CB lymphocytes and the increasing use of reduced intensity conditioning with CBT 4, 8, 9.…”

mentioning

confidence: 99%

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

Sun

Liu

Luo

et al. 2018

Intl Journal of Cancer

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Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single‐arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC‐P) were similar to the MMAC group in the retrospective study (MMAC‐R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies.

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Graft failure in the modern era of allogeneic hematopoietic SCT

Cited by 222 publications

References 56 publications

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

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