Aim. To assess the outcomes of autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic AL Amyloidosis patients treated at the R.M. Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. Materials & Methods. In the period from 2005 to 2022, auto-HSCT was performed in 33 patients with systemic AL Amyloidosis. In 7 of them, auto-HSCT was not preceded by the induction therapy “upfront”. From 2012 all patients received induction therapy prior to transplantation. The median age of patients was 54 years (range 38–68 years); among them there were 17 women and 16 men. Results. The 3-year follow-up period showed hematological response rate of 76 % (95% confidence interval [95% CI] 50–90 %), heart response rate of 27 % (95% CI 6–55 %), renal response rate of 76 % (95% CI 41–93 %), and hepatic response rate of 26 % (95% CI 8–50 %). The 5-year overall (OS) and progression-free (PFS) survivals were 71 % (95% CI 49–85 %) and 53 % (95% CI 32–71 %), respectively. The OS parameters in the group with delayed auto-HSCT, i.e., after induction therapy, were better than in the “upfront” group: 82 % (95% CI 60–93 %) vs. 43 % (95% CI 10–73 %) (p = 0.03). The OS parameters were affected by health status (p = 0.03), reduced left ventricular ejection fraction < 60 % (p = 0.006), stage of heart disease (p = 0.016), and stage III kidney disease (p = 0.007). The PFS parameters depended on ECOG performance status (p = 0.004) and stage of heart disease (p = 0.041). Conclusion. The presented data confirm the results of the studies emphasizing the importance of induction therapy prior to auto-HSCT in the treatment of systemic AL Amyloidosis. More stringent parameters of renal function, left ventricular ejection fraction, and ECOG performance status can be used as criteria for auto-HSCT eligibility. Reduced melphalan doses, as conditioning regimen, can be administered to patients with pronounced comorbidity.

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare and still poorly understood disease in children. It is generally accepted that PNH in children is characterized by severe bone marrow failure, less intensive hemolysis, and less often complicated by thrombosis and organ dysfunction. Aim: to compare the clinical and laboratory characteristics and to determine the long-term prognosis of PNH with disease onset in children and adults. Retrospective and prospective study included patients with active hemolytic PNH, defined by flow cytometry results (clone more than 10% in granulocytes), clinical and laboratory criteria (lactate dehydrogenase (LDH) level above 1.5 of the upper limit of normal (ULN)). The classical PNH and aplastic anemia/PNH (AA/PNH) were studied. A detailed analysis of clinical manifestations, primary diagnoses, complications and overall survival was performed depending on the age of PNH onset (before and after age 18 years). As of August 2018, 355 patients were included in the study (56% female, 44% male) with classic form (49%) and AA/PNH (51%). The median age at the PNH onset and the diagnosis was 27 (5–80) and 30 years (7–80), respectively. The median PNH clone size in granulocytes and red blood cells was 92% and 33%, respectively, and the LDH level of 5.5 ULN. Hemolytic PNH onset during childhood was in 51 patients (14%) with the same frequency of classical form (n = 27; 16%) and AA/PNH (n = 24, 13%) ( p = 0.549). The diagnosis of classical form and AA/PNH was confirmed in childhood in 9 (5%) and 21 (12%) patients respectively. In 81% of classical PNH presenting in children, a misdiagnosis was initially established, and the median time before precise diagnosis was 52 months (4–426). The PNH clone size (median 93% vs 91%, p = 0.321) and hemolysis intensity according to LDH level (median 4.95 vs. 5.76 ULN, p = 0.690) did not differ in children and adults. The frequency of hemolysis symptoms in the onset of the disease correlated with the clone size and was higher in classical PNH compared with AA/PNH, but did not depend on onset age: weakness (98% in children vs. 96% in adults), hemoglobinuria (51% vs 55%), pain (39% vs 45%), jaundice (46% vs 52%), dysphagia (21% vs 28%). The age of PNH onset did not influence the frequency of early (before the diagnosis of PNH) thrombosis (8% vs 13%, p = 0.482) and episodes of acute kidney injury (AKI, 10% vs 9%, p = 0.788). With prolonged follow-up, there is a tendency towards a higher cumulative incidence of thromboses in adults: 5 years 21% vs 12%, 10 years 33% vs 19%, however in the more distant period these differences become insignificant ( p = 0.151). The cumulative incidence of AKI was similar in children and adults: 5 years 16% vs 20%, 10 years 23% vs 22%, respectively ( p = 0.500). The frequency of transfusion dependence, the development of chronic kidney disease and pulmonary hypertension and overall survival were also independent of the PNH onset age. The results of the study in the large cohort of patients indicate the similar clinical profile and a long-term prognosis of active hemolytic PNH in children and adults. Diagnostic errors and late recognition of classical PNH lead to the relative prevalence of AA/PNH in children.

Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare and still poorly understood disease in children. It is generally accepted that PNH in children is characterized by severe bone marrow failure, less intensive hemolysis, and less often complicated by thrombosis and organ dysfunction. Aim: to compare the clinical and laboratory characteristics and to determine the long-term prognosis of PNH with disease onset in children and adults. Retrospective and prospective study included patients with active hemolytic PNH, defined by flow cytometry results (clone more than 10% in granulocytes), clinical and laboratory  criteria (lactate dehydrogenase (LDH) level above 1.5 of the upper limit of normal (ULN)). The classical PNH and aplastic anemia/PNH (AA/PNH) were studied. A detailed analysis of clinical manifestations, primary diagnoses, complications and overall survival was performed depending on the age of PNH onset (before and after age 18 years). As of August 2018, 355 patients were included in the study (56% female, 44% male) with classic form (49%) and AA/PNH (51%). The median age at the PNH onset and the diagnosis was 27 (5–80) and 30 years (7–80), respectively. The median PNH clone size in granulocytes and red blood cells was 92% and 33%, respectively, and the LDH level of 5.5 ULN. Hemolytic PNH onset during childhood was in 51 patients (14%) with the same frequency of classical form (n = 27; 16%) and AA/PNH (n = 24, 13%) ( p = 0.549). The diagnosis of classical form and AA/PNH was confirmed in childhood in 9 (5%) and 21 (12%) patients respectively. In 81% of classical PNH presenting in children, a misdiagnosis was initially established, and the median time before precise diagnosis was 52 months (4–426). The PNH clone size (median 93% vs 91%, p = 0.321) and hemolysis intensity according to LDH level (median 4.95 vs. 5.76 ULN, p = 0.690) did not differ in children and adults. The frequency of hemolysis symptoms in the onset of the disease correlated with the clone size and was higher in classical PNH compared with AA/PNH, but did not depend on onset age: weakness (98% in children vs. 96% in adults), hemoglobinuria (51% vs 55%), pain (39% vs 45%), jaundice (46% vs 52%), dysphagia (21% vs 28%). The age of PNH onset did not influence the frequency of early (before the diagnosis of PNH) thrombosis (8% vs 13%, p = 0.482) and episodes of acute kidney injury (AKI, 10% vs 9%, p = 0.788). With prolonged follow-up, there is a tendency towards a higher cumulative incidence of thromboses in adults: 5 years 21% vs 12%, 10 years 33% vs 19%, however in the more distant period these differences become insignificant ( p = 0.151). The cumulative incidence of AKI was similar in children and adults: 5 years 16% vs 20%, 10 years 23% vs 22%, respectively ( p = 0.500). The frequency of transfusion dependence, the development of chronic kidney disease and pulmonary hypertension and overall survival were also independent of the PNH onset age. The results of the study in the large cohort of patients indicate the similar clinical profile and a long-term prognosis of active hemolytic PNH in children and adults. Diagnostic errors and late recognition of classical PNH lead to the relative prevalence of AA/PNH in children.