1.
Incidence and Outcomes of Respiratory Failure After Non-Myeloablative Related Haploidentical Blood or Marrow Transplant
Stephens, R. S., Psoter, K., Jones, R. J., Merlo, C. A.
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Respiratory failure is a devastating complication of allogenic blood or marrow transplant (BMT). Prior data suggest 20% and 15% of BMT patients develop respiratory failure and ARDS, respectively. Non-myeloablative (NMA) haploidentical BMT allows donor pool expansion and may decrease complications. Incidence, outcomes, and risk factors for respiratory failure after NMA haploidentical BMT are unknown. RESEARCH QUESTION Determine the incidence of respiratory failure after NMA haploidentical BMT and explore outcomes and risk factors for respiratory failure. STUDY DESIGN AND METHODS Single-center, retrospective study of all patients > 18 years old undergoing NMA haploidentical BMT from 2004-2016. The primary outcome was respiratory failure (high-flow nasal cannula oxygen, non-invasive ventilation [NIV], or invasive mechanical ventilation [IMV]) within 2 years after BMT. Respiratory failure incidence is reported as incidence rate ratios (IRR) with 95% confidence intervals. Unadjusted and multivariable Cox proportional hazards models with adjustment for a priori identified patient-level characteristics were used. Results are presented as hazard ratios (HR) with 95% CIs. RESULTS 520 patients underwent NMA haploidentical BMT; 82 (15.8%) developed respiratory failure (IRR 0.114/person-year) at a median of 0.34 years (25(th), 75(th) percentiles 0.06, 0.75 years) after BMT. Older age (HR 1.04, 1.02, 1.07), transplant for MDS (HR 1.99, 1.07, 3.72), and parent donor (HR 3.49, 1.32, 9.26) were associated with increased risk of respiratory failure; higher pre-transplant DLCO (% pred) was associated with lower risk (HR 0.98, 0.77, 0.99). Sixty-one (11.7%) patients required IMV; 30 were successfully extubated. Only 37 (7%) patients had ARDS. Of the 82 with respiratory failure, 43 (52.4%) and 61 (77.2%) died during index hospitalization and by 2 years, respectively. Only 40 (49%) had non-relapse mortality. INTERPRETATION Incidence of respiratory failure and ARDS after NMA haploidentical BMT is modest at 15% by 2 years after transplant. Despite successful extubation in more than 50% of patients, respiratory failure, regardless of cause, is associated with a high rate of death by 2 years, from both relapse and non-relapse causes. Age, BMT for MDS, parental donor, and pre-transplant DLCO were risk factors for respiratory failure.
2.
Thrombotic Microangiopathy after Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis
Imus, P. H., Tsai, H. L., DeZern, A. E., Jerde, K., Swinnen, L. J., BolaƱos-Meade, J., Luznik, L., Fuchs, E. J., Wagner-Johnston, N., Huff, C. A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Transplant-associated thrombotic microangiopathy (taTMA) is a systemic vascular illness associated with significant morbidity and mortality, resulting from a convergence of risk factors after allogeneic blood or marrow transplantation (alloBMT). The diagnosis of taTMA has been a challenge, but most criteria include an elevated lactate dehydrogenase (LDH), low haptoglobin, and schistocytes on peripheral blood smear. We performed a retrospective review of the 678 consecutive adults who received high-dose post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) between January 1, 2015, and August 31, 2018. In April 2016, we initiated a monitoring program of weekly LDH and haptoglobin measurements and blood smears when those 2 parameters were both abnormal on all of our adult patients undergoing alloBMT for hematologic malignancies. During the entire period, the 1-year cumulative incidence of taTMA was 1.4% (95% confidence interval, 0.5% to 2.3%). Eight patients were taking tacrolimus at the time of diagnosis, and 1 was not on any immunosuppression. Eight of 9 patients (89%) were hypertensive. Four patients had invasive infections at the time of diagnosis, 4 patients required renal replacement therapy, and 5 of 9 patients were neurologically impaired. Eculizumab was given to 6 patients (0.9%), of whom 2 died and 4 recovered with resolution of end-organ dysfunction. The paucity of events made the determination of risk factors difficult; however, the low incidence of taTMA in this cohort may be related to the limited use of myeloablative conditioning regimens, low incidence of severe GVHD, and use of PTCy. PTCy-based GVHD prophylaxis appears to be associated with a low incidence of severe taTMA.
3.
Severe cytokine release syndrome after haploidentical peripheral blood transplantation
Imus, P. H., Blackford, A. L., Bettinotti, M., Luznik, L., Fuchs, E. J., Huff, C. A., Gladstone, D. E., Ambinder, R. F., Borrello, I. M., Fuchs, R. J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
INTRODUCTION Inflammatory cytokines released by activated lymphocytes and innate cells in the context of cellular therapy can cause fever, vasodilatation and end organ damage, so-called cytokine release syndrome (CRS). CRS can occur after allogeneic blood or marrow transplantation, but especially after HLA-haploidentical (haplo) peripheral blood transplantation (PBT). We reviewed charts of all patients who underwent haplo PBT between October 1, 2013 and September 1, 2017 and graded CRS. A total of 146 consecutive related haplo PBTs were analyzed. CRS occurred in 130 (89%) of the patients, but most was of mild (Grades 0-2) severity. Severe CRS (Grades 3-5) occurred in 25 patients (17% of PB haploPBT). In this group with severe CRS, 13 had encephalopathy; 12 required hemodialysis, and 11 were intubated. Death from the immediate complications of CRS occurred in 6 patients (24% of the severe CRS group and 4% of the entire haplo PBT cohort). The cumulative probability of non-relapse mortality (NRM) for patients with severe CRS was 38% at 6 months; it was 8% in the 121 out of 146 patients without severe CRS. In conclusion, CRS occurs in nearly 90% of haploidentical peripheral blood stem cell transplants. Older recipients (OR 2.4, 95% CI 0.83-6.75, p=0.11) of haploidentical PBT and those with a history of XRT (OR=3.85, 95% CI 1.32-11.24, p=0.01) have a higher risk of developing severe CRS. Most recipients of haplo PBT develop CRS, but less than 20% experience severe complications. The development of severe CRS significantly increases NRM.