News

Both MAC and RIC are valid options for PTCy-Haploidentical PBSC Transplantation

Sugita J, Kagaya Y, Miyamoto  T  et al.  Myeloablative and reduced-intensity conditioning in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Using Post-Transplant Cyclophosphamide. Bone Marrow Transplantation: published online 08/07/18  (doi: 10.1038/s41409-018-0279-1).
Investigators found that myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) both represent safe and effective choices for HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCY-haploPBSCT). The finding applies to adults with hematologic malignancies, reports the Japan Study Group for Cell Therapy and Transplantation, after performing a pair of Phase II trials. The primary outcome, defined as event-free survival (EFS) at 1 year, was 64% of the 50 patients who underwent MAC and 43% of the 77 participants who underwent RIC. Overall survival and EFS at 2 years was 68% and 54%, respectively, in the MAC cohorts and 44% and 35%, respectively, in the RIC groups.  Only 8% of the MAC population and 5% of the RIC population developed grades III-IV acute graft-versus-host disease, and the rate of nonrelapse mortality was limited to 10% in the former and 20% of the latter. A total of 36% of MAC participants and 45% of RIC participants relapsed by year 2.   Among those surviving without relapse,  83% and 86%, respectively, discontinued immunosuppressant therapy by 2 years.

Read More - May Require Paid Subscription

High levels of AREG refines aGVHD clinical risk score

Holtan SG, DeFor TE, Panoskaltsis-Mortari  A,  et al. Amphiregulin Modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: Results from BMT CTN 0302/0802. Blood Advances. 2018; 2 (15): 1882.
High-circulating amphiregulin (AREG) stratifies patients into high-risk subgroups, effectively fine-tuning the Minnesota acute graft-versus-host disease (aGVHD) clinical risk score. The researchers previously observed that circulating AREG rises in late-onset aGVHD and subsequently sought to establish its clinical relevance in the context of aGVHD risk. Using 251 aGVHD onset blood samples from the Blood and Marrow Clinical Trials Network (BMT CTN) primary treatment trials, the team examined the relationship between AREG and GVHD severity, day 28 complete or partial response (CR/PR) to first-line therapy, overall survival (OS), and nonrelapse mortality (NRM). Every doubling of plasma AREG was correlated with a 33 percent reduction in likelihood of day 28 CR/PR. An AREG threshold of 33 pg/mL was associated with a lower rate of steroid response, higher NRM, and inferior OS rates. If verified in larger studies, measuring AREG at aGVHD onset could add value in risk-stratifying patients with aGVHD.

Read More

Comorbidity Impact on Non-Relapse Mortality

Fein JA, Shimoni  A, Labopin M, et al. The Impact of Individual Comorbidities on Non-Relapse Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation. Leukemia. 2018; 32: 1787.
Renal dysfunction, hypoalbuminemia, and severe hepatic disease were associated with the highest risk of non-relapse mortality (NRM) following allogeneic stem cell transplantation (allo-SCT), according to a retrospective study of whether individual comorbidities could better define NRM risk. The researchers also theorized that the hazard of comorbidities is exerted in a regimen-specific manner, in view of differing toxicity profiles of conditioning agents. The study population included 875 adults treated with an allo-SCT, and six conditioning regimens examined. The hazard ratio (HR) for NRM associated with individual comorbidities was calculated using multivariable Cox regressions across the entire group and within each regimen. The risk associated with specific comorbidities was tweaked by the conditioning regimen and did not correlate with intensity. NRM risk was elevated with cardiac disease in subjects conditioned with fludarabine/busulfan. Severe pulmonary disease and a pre-existing infection were tied to higher NRM risk in patients receiving fludarabine/melphalan and fludarabine/treosulfan, respectively. Comorbidities may have an impact that is specific to particular conditioning regimens, implying that regimen selection should be partly dictated by specific comorbidities.