Haematopoietic stem-cell transplantation: Case

Framing the case

This six-year-old boy is on day fourteen of an allogeneic matched unrelated donor transplant, with the weight gain, the tender hepatomegaly and the rising bilirubin that together point to the hepatic sinusoidal obstruction syndrome. The timing, within the first twenty-one days of the myeloablative conditioning, the total body irradiation and the etoposide, is the classic window for the syndrome, and the weight gain of eight percent from the baseline alongside the tender liver and the jaundice meets the diagnostic triad. The framework is the recognition that this is a hepatotoxic complication of the conditioning, distinct from the graft-versus-host disease and the drug injury, and that the early recognition and the prompt defibrotide are the decisive interventions. [8]

The differential and the diagnostic pathway

The hepatic differential at this point is the sinusoidal obstruction syndrome against the hepatic graft-versus-host disease, the drug-induced liver injury from the antifungal or the antibiotic, and the viral hepatitis. The sinusoidal obstruction syndrome presents early, within the first twenty-one days, with the weight gain and the tender liver, while the hepatic graft-versus-host presents later, often after the engraftment, with the jaundice and the gut involvement. The diagnosis of the sinusoidal obstruction syndrome is clinical, supported by the ultrasound with the doppler showing the reversal of the portal flow and the elevated hepatic pressures, with the transjugular liver biopsy and the pressure measurement in the selected case. The viral studies exclude the cytomegalovirus and the hepatitis, and the drug history excludes the reaction. [8][1]

The management of the sinusoidal obstruction syndrome

The defibrotide is started at once at twenty-five milligrams per kilogram per day in four divided doses, given as the intravenous infusion over two hours every six hours, for a minimum of twenty-one days and continued until the resolution plus a further seven days. The fluid restriction and the diuretics manage the ascites and the weight gain, the renal function is supported, and the coagulopathy is corrected with the fresh frozen plasma and the vitamin K. The thrombocytopenia is supported with the platelet transfusion, and all the blood products are irradiated and leucodepleted throughout. The child with the hepatorenal syndrome or the respiratory failure from the fluid overload is moved to the intensive care. The severe form carries a mortality of over eighty percent when untreated, and the defibrotide cuts this sharply when started early. [10]

The engraftment and the febrile neutropenia

Through the cytopenia, the boy is monitored for the engraftment and the febrile neutropenia. The neutrophil engraftment is the first of three consecutive days with an absolute neutrophil count of zero point five times ten to the nine per litre or above, and the platelet engraftment is seven consecutive days above twenty times ten to the nine per litre without the transfusion support. The donor chimerism, checked at the defined intervals, confirms that the engrafting cells are the donor's. The fever in the child with a neutrophil count under zero point five times ten to the nine per litre is the febrile neutropenia, and the antipseudomonal beta-lactam is given within one hour after the blood cultures, with the empiric escalation for the unstable child. [11][12]

The acute graft-versus-host disease and the prophylaxis

The engraftment period is also the window for the acute graft-versus-host disease, and the boy is monitored for the rash on the palms and soles, the diarrhoea and the bilirubin rise. The prophylaxis he received, the calcineurin inhibitor with the methotrexate or the post-transplantation cyclophosphamide, is reviewed. The established acute graft-versus-host disease is treated with the immunosuppression graded to the severity, with the systemic glucocorticoid for the grade three to four disease and the ruxolitinib for the steroid-refractory form. The tissue biopsy confirms the graft-versus-host before the escalation of the immunosuppression, because the empiric treatment of a misdiagnosed infection is as harmful as the missed graft-versus-host. [4]

The family counselling and the long-term plan

The family is counselled on the intent of the transplant, the conditioning toxicity, the engraftment period and the long-term complications. The total body irradiation raises the risk of the growth impairment, the gonadal failure, the hypothyroidism, the cataract and the second malignancy, and the boy is enrolled in the late-effects clinic for the lifelong surveillance. The fertility preservation is addressed before the gonadotoxic conditioning, and the endocrine, the cardiac and the pulmonary function are monitored through the survivorship. The family is taught the neutropenic precautions, the strict return-with-fever rule, and the irradiated-product requirement, and the boy is supported through the long immunosuppression and the psychological burden of the treatment. [1][8]