Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyper-inflammatory syndrome with prolonged high fever, hepatosplenomegaly, pancytopenia, hepatic dysfunction, low fibrinogen level, hypertriglyceridemia and hemophagocytosis in the bone marrow, liver, spleen, or lymph nodes. Broadly, HLH can be classified into either primary or secondary HLH. The familial HLH (FHL) is an autosomal recessive disorder with a median survival of less than two months after diagnosis if untreated, and that typically has its onset during infancy or early childhood. Secondary HLH (sHLH) may occur in association with severe infections, malignancies or autoimmune diseases, although it may subside spontaneously, it may also be associated with pronounced mortality. The most present therapeutic regimes such as HLH-2004 protocol and allogene hemopoietic stem cell transplantation (allo-HSCT) have been designed for the primary, inherited disease FHL, in patients aged <18 years, as well as any severe form of HLH. Reports on the treatment of sHLH are rare, and no standard treatment protocol is as yet established. We implemented prednisone, vincristine, cyclophosphamide (COP) combined chemotherapy in treating adult hemophagocytic lymphohistiocytosis (HLH) and observed the therapeutic efficacy. Fifteen patients, among whom 7 were infection-associated HLH (IHLH), 4 had no apprent underlying causes, lymphoma-associated HLH (LHLH) and autoimmune disease-associated HLH took up of 2 respectively, were enrolled in our study. The initial therapy of COP protocol included cyclophosphamide (CTX) 0.3 g/m2 i.v. and vincristine (VCR) 1.4 mg/m2 i.v., once weekly for the first eight weeks, prednisone (PRED) 60 mg/m2/d p.o., for the first 2 weeks, and reduced by 50% of the previous dose every 2 weeks until the end of the 7th week, then progressively tapered it for 1 week. A continuation therapy of COP was CTX 0.3 g/m2 i.v., on day 1, day 8; VCR 1.4 mg/m2 i.v., on day 1, day 8; PRED 20 mg/m2 p.o. for 14 days and it was repeated every 4 weeks for a total of 4 to 6 cycles in responding. Patients were given COP protocol individually depending on their different etiologies and responses to therapy. With a mean follow-up of 72.5 weeks, the median overall survival (OS) was 43 weeks and the one-year probability of overall survival (OS) was 10/15(66.7%). The overall response rate was 80.0%, consisting of seven (46.7%) complete response (CR) and five (33.3%) partial response (PR). Different etiology induced HLH had different sensitivity and response rate to COP chemotherapy. Hematological and non-hematological toxicities were predominantly grade I or II and most patients could well tolerate without requiring a dose reduction of full-dose COP. In conclusion, as a mild and cost-effective chemotherapy, COP protocol showed a relatively favorable effect for adult patients with sHLH. In the following situations, like some with bacteria infection, some arose from an autoimmune disease, or else some who can not endure an intensive chemotherapy due to an old age or disease severity, the COP protocol may be the first choice.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.