Haematopoietic stem-cell transplantation: Viva

Framing the problem

This girl is eighteen days after a matched unrelated donor transplant, which places her in the engraftment period when both the acute graft-versus-host disease and the sinusoidal obstruction syndrome declare themselves. The rash on the palms and soles points toward the acute graft-versus-host disease, while the tender liver points toward the sinusoidal obstruction syndrome, and the rising bilirubin is common to both. The framework is the recognition that these two complications may coexist, that each has a specific therapy, and that the tissue diagnosis settles the question before the empiric treatment is escalated. The first priority is to resuscitate the unstable elements and to confirm the cause. [5]

The differential and the diagnostic pathway

The examiner will probe the differential, and the candidate must separate the graft-versus-host from the sinusoidal obstruction syndrome and from the mimics. The acute graft-versus-host disease presents with the rash, the diarrhoea and the bilirubin rise, and it is graded by the extent of the skin, the bilirubin level and the stool volume. The sinusoidal obstruction syndrome presents with the weight gain, the tender hepatomegaly and the jaundice within the first twenty-one days, and it is supported by the ultrasound with the reversal of the portal flow. The drug eruption and the viral hepatitis add to the differential. The skin and the liver biopsy settle the graft-versus-host, and the ultrasound and the hepatic pressures settle the sinusoidal obstruction syndrome. [8][5]

The management of the acute graft-versus-host disease

If the biopsy confirms the acute graft-versus-host disease, the management is the immunosuppression graded to the severity. The grade one to two disease is treated with the topical glucocorticoid and the optimisation of the calcineurin inhibitor, while the grade three to four disease is treated with the systemic glucocorticoid at one to two milligrams per kilogram per day of the methylprednisolone. The steroid-refractory disease, the progression after a week or the failure to respond after two weeks, is treated with the ruxolitinib, the Janus kinase inhibitor. The graft-versus-host prophylaxis that failed is reviewed, and the family is counselled on the long course of the immunosuppression. [5][4]

The management of the sinusoidal obstruction syndrome

If the ultrasound and the clinical picture confirm the sinusoidal obstruction syndrome, the defibrotide is started at once at twenty-five milligrams per kilogram per day in four divided doses, 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, the renal function is supported, and the coagulopathy is corrected. The severe form carries a mortality of over eighty percent when untreated, and the defibrotide cuts this sharply when started early. The examiner will ask about the risk factors, the prior hepatotoxic therapy and the iron overload, and about the prophylaxis for the high-risk child. [10]

The engraftment and the chimerism

The examiner will turn to the engraftment, and the candidate must hold the milestones. 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, measured by the short tandem repeat analysis, confirms that the engrafting cells are the donor's, and a falling donor chimerism flags the graft rejection and the impending graft failure. The candidate who can read the day from the transplant alongside the symptom holds the framework for every post-transplant scenario. [11]