Clinical options after failure of allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies

Petrović, Aleksandra; Hale, Gregory A.

doi:10.1586/eci.11.24

Cited by 10 publications

(6 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growth factors are often administered though there is little supporting evidence. Frequently they do not improve counts in primary GF and are not a long term-solution Donor Lymphocyte Infusions (DLI) may have a role in the context of falling donor chimerism and can convert some patients to full donor chimerism and remedy secondary GF; however, this is case-dependent and there are no reports specific to MF (52) Recipients with primary GF with no functional haematopoiesis and pancytopaenia should be considered for a second allo-HCT using either the same or an alternative stem cell donor chimerism. This can successfully treat poor graft function and does not require further conditioning.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

et al. 2021

View full text Add to dashboard Cite

Allogeneic Haematopoietic Cell Transplantation (allo-HCT) remains the only curative approach in Myelofibrosis (MF). Despite advances over recent decades, relapse and non-relapse mortality rates remain significant. Relapse rates vary between 15% and 25% across retrospective studies and management strategies vary widely, ranging from palliation to adoptive immunotherapy and, in some cases, a second allo-HCT. Moreover, in allo-HCT, there is a higher incidence of poor graft function and graft failure due to splenomegaly and a hostile 'pro-inflammatory' marrow niche. The Practice Harmonisation and Guidelines subcommittee of the Chronic Malignancies Working Party (CMWP) of EBMT convened an international panel consisting of transplant haematologists, histopathologists and molecular biologists to propose practical, clinically relevant definitions of graft failure, poor graft function and relapse as well as management strategies following allo-HCT. A systematic approach to molecular monitoring, histopathological assessment and chimerism testing is proposed. These proposed recommendations aim to increase the accuracy and uniformity of reporting and to thereby facilitate the development of more consistent approaches to these challenging issues. In addition, we propose management strategies for these complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A longer interval from transplant to relapse is associated with reduced risk of death [5]. Therefore, maximizing the duration of remission is an important treatment goal [6], and novel therapeutic strategies are needed to provide long-term disease control and extend remission in the post-transplant setting.…”

Section: Introductionmentioning

confidence: 99%

CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes

Lima

Oran

Champlin

et al. 2018

Biology of Blood and Marrow Transplantation

130

View full text Add to dashboard Cite

Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve post-transplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy after alloSCT. Adults with MDS or AML in morphologic complete remission at CC-486 initiation (42 to 84 days after alloSCT) were included. Patients received 1 of 4 CC-486 dosing schedules per 28-day cycle for up to 12 cycles. Endpoints included safety, pharmacokinetics, graft-versus-host disease (GVHD) incidence, relapse/progression rate, and survival. Of 30 patients, 7 received CC-486 once daily for 7 days per cycle (200 mg, n = 3; 300 mg, n = 4) and 23 for 14 days per cycle (150 mg, n = 4; 200 mg, n = 19 [expansion cohort]). Grades 3 to 4 adverse events were infrequent and occurred with similar frequency across regimens. Standard concomitant medications did not alter CC-486 pharmacokinetic parameters. Three patients (10%) experienced grade III acute GVHD and 9 experienced chronic GVHD. Of 28 evaluable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) who had received 7-day dosing and 3 of 23 (13%) who had received 14-day dosing. Transplant-related mortality was 3%. At 19 months of follow-up, median overall survival was not reached. Estimated 1-year survival rates were 86% and 81% in the 7-day and 14-day dosing cohorts, respectively. CC-486 maintenance was generally well tolerated, with low rates of relapse, disease progression, and GVHD. CC-486 maintenance may permit epigenetic manipulation of the alloreactive response postallograft. Findings require confirmation in randomized trials. (ClinicalTrials.gov NCT01835587.).

show abstract

“…In most situations, treatment options at relapse after HCT are very limited with unacceptably high rates of disease relapse. The treatment options for disease relapse after HCT include withdrawal of immune suppression, chemotherapy, second allogeneic transplant, cytokine and adoptive cell therapy and donor lymphocyte infusion [1].…”

Section: Introductionmentioning

confidence: 99%

Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant

et al. 2019

View full text Add to dashboard Cite

BackgroundSecond allogeneic hematopoietic stem cell transplant (HCT) remains as an option for disease relapse after initial HCT.MethodsWe analyzed retrospectively the outcomes of 65 consecutive patients who underwent a second HCT for disease relapse at the University of Chicago. Univariate and multivariate analysis were conducted, and a scoring system was generated to select the patients who would benefit second HCT.ResultsAll except four patients received T cell depleted (TCD) first HCT. The majority of patients had AML (n = 47) and high risk MDS (n = 5). The median age at second HCT was 45 years (11–73). 13 patients (20%) achieved CR before second HCT. 98% (n = 64) and 72% (n = 47) patients achieved neutrophil and platelet engraftment at a median interval of 10 and 18 days, respectively, following the second HCT. With a median follow up of 23 (5.5–140) months for survivors after second HCT, the estimated 2 years PFS was 17.5% and the 2 years OS was 22.6%. The day 100 cumulative incidence of non-relapse mortality rate was 23.6%, and the cumulative incidence of aGVHD and cGVHD were 16.9% and 7.7% respectively at 1 year after second HCT. In univariate analysis, patients with remission duration after first HCT of > 12 months and those in CR before second HCT had significantly better PFS and OS. A scoring system using disease status before second HCT (CR = 0 vs. non-CR = 1), and remission duration after first HCT (< 6 = 2, 6–12 = 1 and > 12 months = 0) was generated as an approach to classify patients into different risk categories in the purpose to provide guidance to the transplant physician to inform the outcomes to potential patients undergoing 2nd HCT. A score of < 2 (n = 26) identified a group with PFS and OS of 31.6% and 36.2% at 2 years after second HCT.ConclusionIn conclusion, second HCT is a viable option for disease relapse after TCD HCT for patients entering second HCT in remission and/or remission duration > 12 months after first HCT with acceptable rates of GVHD and donor engraftment.

show abstract

Clinical options after failure of allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies

Cited by 10 publications

References 97 publications

Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes

Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant

Contact Info

Product

Resources

About