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Systematic Review of Signs and Symptoms Associated with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy
Dandoy, C. E., Tsong, W. H., Sarikonda, K., McGarvey, N., Perales, M. A.
Transplantation and cellular therapy. 2022
Abstract
INTRODUCTION Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplant process that has consistently been associated with a substantial increase in morbidity and mortality compared to HSCT patients who do not develop TMA. The objective of this study is to systematically review published signs and symptoms of HSCT-TMA and compare HSCT-TMA patients to HSCT patients who do not develop TMA. METHODS Publications were identified using multiple search term variations for stem cell transplant that were entered into PubMed, Embase, and CINAHL databases. Two reviewers screened references at the abstract level before reviewing full text against inclusion and exclusion criteria using a PICOS-T framework. Complication proportions were grouped by organ class, then complication type. Meta-analyses were conducted using a random-effects model in Review Manager 5.4. RESULTS A total of 30 studies were included after 2,338 references were screened. The majority (n=23 [14 adult, 5 pediatric, 4 both]) of studies examined allogeneic transplants only. Four studies examined autologous transplant only (all pediatric). Three studies included both transplant types (all pediatric). HSCT-TMA was associated with renal dysfunction (OR 11.04 adult, allogeneic; 7.35 pediatric, all transplants), renal failure (OR 2.41 adult and pediatric, allogeneic), renal replacement therapy (OR 6.99 pediatric all transplants; 60.85 adult, allogeneic), and hypertension (OR 5.44 adult, allogeneic). HSCT-TMA was associated with respiratory failure (OR 8.00 adult and pediatric, allogeneic), pulmonary hypertension (OR 9.86 adult and pediatric, allogeneic), pleurocentesis requirement (OR 5.45 pediatric, all transplants), non-invasive ventilation (OR 6.15 pediatric, all transplants), and invasive mechanical ventilation (OR 5.18 pediatric, all transplants). Additionally, HSCT-TMA was associated with neurological symptoms (OR 2.28 adult and pediatric, allogeneic), pericardial effusion (OR 2.56 adult and pediatric, allogeneic; OR 8.76 pediatric, all transplants), liver injury (OR 3.87 adult, allogeneic), infection (OR 9.25 adult, allogeneic; 2.06 pediatric, all transplants), gastrointestinal bleed (OR 7.78 adult and pediatric, allogeneic), and acute graft versus host disease (grades 3-4) (OR 3.29 adult and pediatric, allogeneic). DISCUSSION This study represents the first systematic review of HSCT-TMA signs and symptoms. Current diagnostic criteria systems involve laboratory markers for multi-organ dysfunction, including renal dysfunction, liver injury, and general tissue damage. Some diagnostic criteria include neurological symptoms, increased need for transfusions, and hypertension. This study identified additional associations with HSCT-TMA, including increased pulmonary hypertension, respiratory failure, fever, gastrointestinal bleeding, and pericardial effusion. These symptoms might be included for evaluation in future diagnostic criteria and current practice.