A case of relapsed refractory autoimmune haemolytic anaemia followed by refractory idiopathic thrombocytopenic purpura treated with stem cell transplantation

The patient presented to the hospital at the age of 11 months with severe warm-reactive
autoimmune haemolytic anaemia, renal failure, transaminitis, mild asymptomatic
thrombocytopenia, elevated D-dimer levels. Infectious causes, haemolytic uremic syndrome
was excluded. Anti-DNA, anti-ds-DNA were negative, no PNH clone was detected. The boy
received therapy with methylprednisolone and azathioprine. At the age of 2 year 7 months
the patient presented with severe onset of cold-reactive autoimmune haemolytic anaemia,
jaundice, livedo reticularis, hepatosplenomegaly, transaminitis. We treated him with
methylprednisolone pulse therapy, high dose of intravenous immunoglobulins (IVIG),
rituximab, azathioprine, cyclophosphamide 500mg/m2, mycophenolate mofetil and
fludarabine. After adding fludarabine the haemolysis subsided. Investigations of classical
and alternative complement pathways revealed no pathology. Next generation sequencing
showed no primary immune deficiency. Most autoimmunity markers were negative,
antibodies to beta-2-glycoprotein were temporary positive. No double negative T-cells were
detected, B12 vitamin level was normal. In 3 months the patient had transient toxic
hepatitis, immunosuppressive therapy (IST) was discontinued due to agranulocytosis and
bone marrow stromal damage. 3 months after discontinuation of IST, the patient presented
with idiopathic thrombocytopenic purpura (ITP), refractory to treatment. The patient
received methylprednisolone pulse-therapy, dexamethasone, IVIG, azathioprine, rituximab,
cyclophosphamide, vincristine, daily thrombocyte transfusions. Despite the broad IST and
transfusions, the boy’s thrombocyte counts were continuously below 2000/μL. He had
severe skin and mucosal haemorrhages with macrohematuria and epistaxis. Antithrombocyte antibodies were negative, no double negative T-cell population was detected.
Leukocyte counts and haemoglobin levels at presentation of ITP were within normal range.
Beta-2-glycoprotein, transaminases were within normal range. Slowly the patient’s condition
improved. In July 2019 stem cell transplantation from HLA-identical sibling was performed,
partial chimerismus 70/30 donor to recipient is detected without any clinical signs.