Hemophagocytic lymphohistiocytosis: review of etiologies and management

George, Melissa R

Virtually all genetic cases of HLH and many secondary cases should be treated with HSCT. The first report of successful HSCT was reported in 1986. 252 Several studies have demonstrated that HSCT is the only true hope for permanent control of the disease or essentially a cure. [253] [254] [255] [256] [257] A study of 86 children treated with HLH-94 followed by HSCT demonstrated similar long-term disease-free survival (70% at 3 years) with matched unrelated donor transplants as with matched sibling transplants. Survival with family haploidentical donor transplants or mismatched unrelated transplants showed much less favorable results with long-term disease-free survival of only 50%. 258 Cord blood transplant has been successful in some patients. However, overall transplant morbidity and mortality remains high. The same pediatric study showed a mortality rate of 26 out of 86 patients, with deaths resulting from pulmonary and liver complications. 258 Patients responding well to pretransplant induction therapy appear to respond best to HSCT. Pre-transplant conditioning regimens generally include busulfan, etoposide, and cyclophosphamide. Busulfan levels must be carefully monitored, and clonazepam or phenytoin may be useful as anticonvulsive prophylaxis. Dexamethasone may be used to prevent VP-16-induced anaphylactic-like symptoms. Mesna can be used for protection against cyclophosphamideinduced bladder injury. Trimethoprim/sulfamethoxazole may be used for pneumocystis prophylaxis, and acyclovir prophylaxis is recommended. 7 Acute graft versus host disease (GVHD) appears to be the most common complication post-transplant, with rates as high as 32% and chronic GVHD rates at about 9%. 259 Additionally, some patients may develop mixed chimerism necessitating regular donor lymphocyte infusions. 30 With reduced intensity conditioning at an experienced transplant center, patients surviving to HSCT have an approximate survival rate of 92%. 202 The unifying thread of all treatments is that the best success rates occur when complete remission is achieved rapidly and HSCT closely follows.