Clinical usefulness of diagnostic criteria for transplant-associated thrombotic microangiopathy
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ORIGINAL ARTICLE
Clinical usefulness of diagnostic criteria for transplant‑associated thrombotic microangiopathy Ken Sagou1,2 · Nobuaki Fukushima1 · Shun Ukai1 · Miyo Goto1 · Kazutaka Ozeki1 · Akio Kohno1 Received: 11 June 2020 / Revised: 21 July 2020 / Accepted: 28 July 2020 © Japanese Society of Hematology 2020
Abstract One major cause of treatment-related death is transplant-associated thrombotic microangiopathy (TA-TMA). Because of difficulties with diagnosis, many criteria for TA-TMA have been defined. Some patients clinically suspected as TA-TMA have been treated as TA-TMA regardless of TA-TMA criteria fulfillment (clinical-TMA). To examine sensitivities of TATMA criteria for clinical-TMA, we retrospectively evaluated 160 patients undergoing allogeneic hematopoietic stem cell transplantation by five major TA-TMA criteria and compared them with clinical-TMA. Cumulative incidences of TA-TMA and non-relapse mortality (NRM) were widely diverse between criteria. Thirty-eight patients fulfilled one or more TA-TMA criteria (total-TMA), and 12 of them fulfilled only one criterion. In patients with total-TMA, thrombocythemia, serum creatinine > 1.5 × baseline, and proteinuria were especially repeatedly observed among TA-TMA criteria. Ninety-two percent of clinical-TMA patients were classified as patients with total-TMA, and high NRM incidences were exhibited in patients with total-TMA even without clinical-TMA. Hematopoietic cell transplant-comorbidity index ≥ 3, nutritional risk index 2 × baselinea Negative
IWG-TMA [5]
O-TMA [6]
> 4% Elevated
≥ 2/HPF Elevated
Present Present Decreased
Negative Present Present Decreased
COH-TMA [7] b
Present > 2 times of ULN Cre > 1.5 × baseline Present
HPF high-power field, LDH lactate dehydrogenase, ULN upper limit of normal, Cre serum creatinine, CCr creatinine clearance a
Neurologic dysfunction instead of renal dysfunction was accepted for diagnosis
b
Schistocytes need to be present at two consecutive smears
13
CCH-TMA [8] Present Elevated Proteinuria Negative Present Present Hypertension
Clinical usefulness of diagnostic criteria for transplant-associated thrombotic…
Our strategy for initial treatment of TA-TMA was withdrawal of CNIs with substitution by corticosteroid [4]. Further treatment was not standardized and depended on physicians’ decision.
Other definitions Disease risk was classified according to the refined disease risk index proposed by Armand et al. [11] The hematopoietic cell transplant-comorbidity index (HCT-CI) was scored according to the report by Sorror et al. [12] The nutritional risk index (NRI) was calculated at nearest time point prior conditioning regimen as previously described [13]. The myeloablative and reduced-intensity conditioning regimens were defined according to the National Marrow Donor Program/Center for International Blood and Marrow Transplant Research operational definitions criteria [14]. GVHD prophylaxis consisted of tacrolimus or cyclosporine and short-term methotrexate, but in cases of HSCT from haploidentical rel
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