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SCID Genotype and Post-Transplant CD4 Count Predict Survival, Immune Recovery
Haddad E, Logan BR, Griffith LM, et al. SCID Genotype and 6-Month Post-Transplant CD4 Count Predict Survival and Immune Recovery. Blood. 2018; (doi: 10.1182/blood-2018-03-840702).
This retrospective study conducted by the Primary Immune Deficiency Treatment Consortium showed that among 662 patients with Severe Combined Immunodeficiency (SCID) given a hematopoietic cell transplant (HCT) from 1982-2012 the SCID genotype and the CD4+ and CD4+CD45RA+ cell counts 6 and 12 months post-HCT were predictive of overall survival and long-term T-cell reconstitution. Best survival was observed among those receiving HCT from  matched sibling donors (MSDs). Multivariate analysis showed that SCID genotype strongly influenced survival and immune reconstitution among those receiving non-MSD HCT. Those with SCID genotypes of RAG, IL2RG or JAK3 had better survival, but those with RAG or DCLRE1C had poorer immune reconstitution.  Infection-free status and younger age at HCT were associated with improved survival. Patients receiving a conditioning regimen (reduced intensity or myeloablative) had better T and B cell reconstitution than those receiving only immunosuppression or no conditioning therapy.  Thus, SCID genotype should be considered when planning treatment.  Close follow-up of immune reconstitution after HCT is needed to identify patients who may require additional intervention to prevent poor long-term outcome.

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Fludarabine, Busulfan, and Low-Dose TBI Conditioning for Adult ALL Transplant
Speziali C, Daly A, Abuhaleeqa M, et al. Fludarabine, Busulfan, and Low-Dose TBI Conditioning Versus Cyclophosphamide and TBI in Allogeneic Hematopoietic Cell Transplantation. Leukemia & Lymphoma. 2018; (doi: 10.1080/10428194.2018.1493734).
Researchers found encouraging outcomes following a conditioning regimen of fludarabine, busulfan, and low-dose total body irradiation (TBI) for adults with acute lymphoblastic leukemia (ALL).   The study compared outcomes of 74 adults with ALL given conditioning with cyclophosphamide and TBI (CY/TBI) with 72 adults with ALL given fludarabine, busulfan, and 400 cGy TBI (Flu/Bu/TBI) in combination with anti-thymocyte globulin.  Of interest, the non-relapse mortality was similar between the two groups even though the patients in the Flu/Bu/TBI group had poorer performance status pre-HCT.  Post-transplant relapse rates were also similar between the two groups which resulted in similar overall and progression-free survival.  This study suggests that Flu/Bu/TBI may be a reasonable conditioning regimen to consider for adults with ALL who have poor performance pre-HCT.

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Improved survival with Thiotepa-Based Intensified RIC for Adult Double-Unit CBT
Sharma P, Pollyea DA, Smith CA, et al. Thiotepa-Based Intensified RIC Adult Double-Unit CBT Results in Decreased Relapse Rate. Biology of Blood and Marrow Transplantation. 2018; 24 (8): 1671 (doi: 10.1016/j.bbmt.2018.04.019).
Researchers found in this retrospective cohort study that a reduced-intensity conditioning (RIC) regimen including thiotepa resulted in improved outcomes among adult patients receiving double-unit cord blood transplant (CBT). Standard RIC with fludarabine, cyclophosphamide, and low-dose total body irradiation (TBI) is well-tolerated but is associated with high relapse rates. To investigate whether intensifying RIC could reduce relapse without increasing transplant-related mortality (TRM) results from 52 adults who received standard RIC were compared with 47 adults given intensified RIC regimen of fludarabine, cyclophosphamide, thiotepa and low-dose TBI in this retrospective CBT study. The results showed a lower relapse rate and higher overall survival rate for those given the intensified regimen. The incidence of grade III to IV acute graft-versus-host disease (GVHD) and any chronic GVHD was similar between the two groups.  There was also no between-group difference in TRM. Based on these findings, the researchers suggest adding thiotepa to standard RIC may improve outcomes for recipients of double-unit CBT.

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Cardiac Function Effects of CD19 CAR T Cell Therapy in Children
Burstein DS, Maude S, Grupp S, et al. Cardiac Profile of Chimeric Antigen Receptor T Cell Therapy in Children. Biology of Blood and Marrow Transplantation. 2018; 24 (8): 1590 (doi: 10.1016/j.bbmt.2018.05.014).
Researchers report that while 10% of children with acute lymphoblastic leukemia see systolic function deteriorate after CD19 chimeric antigen receptor (CAR) T cell therapy, it is rarely a lasting effect. While the major toxicities of CAR T cell therapy are cytokine release syndrome often accompanied by decreased blood pressure, this study further characterizes the cardiovascular effects associated with CAR-T therapy.   Investigators from Children's Hospital of Philadelphia reviewed all 98 patients at the institution who received CD19 CAR T cell therapy between April 2012 and September 2016. There were 24 patients who had hypotension requiring inotropic support between 1-9 days (mean 4.6 days) after CAR T cell infusion and 10 patients had worsening systolic function.  It was found that pre-CAR T treatment marrow blast count of >25% or pre-existing cardiac dysfunction which were associated with development of serious hypotension but not having received prior total body irradiation nor prior anthracycline dose.  This study identifies a group of CAR T recipients at high risk for serious hypotension who may warrant close observation.