Jurnal Internasional HLH: menonton dan menunggu, atau bertindak dan menyembuhkan?
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HLH patients, whether children or adults, are the most difficult to diagnose and challenge to treat patients treated by hematology / oncology specialists. Overall survival is 50% to 60% whether the patient has a mutation that causes HLH or not. 2 3 Delay in diagnosis, inadequate response to initial therapy or rescue, infection, and damage to organs associated with inflammation contribute to this poor outcome. HLH patients with mutations best treated with hematopoietic stem cell transplantation (HSCT) after disease control are achieved by treatment with decadron and etoposide. In the process of identifying a donor suitable for HSCT, one can find a sibling who is an AC with the same biasial mutation responsible for HLH in the IC. Until the report by Lucchini et al., Doctors did not have the data to tell them about whether it was better to do HSCT before or after AC had developed HLH. Although transplant-related deaths (TRM) have increased markedly with reduced intensity conditioning, this is still very significant, and convincing parents and insurance companies to continue transplanting healthy children is an ethical dilemma. 4 The most striking fact of this article is that 15 of the 16 AC transplanted before HLH development survived compared to only 6 out of 10 transplants after HLH development, a statistically significant difference even with small numbers of patients (see picture). The authors emphasize that patients with perforin mutations are most likely to activate early in life, as has been reported by others, 5 6 so that making ACs with prospective mutations is ideal for early HSCT. . Those with the MUNC 18-2 mutation are known to be present in the elderly and have milder HLH forms, probably because they can restore natural killer cell activity after chemotherapy and can be observed to see if an HSCT is really needed.  7 Only 1 in 5 ACs with MUNC 18-2 deficiency develop HLH, with 2/5 now almost 4 years without evidence of HLH. MUNC 18-2 deficiency, although the second most common HLH mutation, is the one with the most complex clinical phenotype because wild-type ectopic expression STXBP2 can overcome MUNC deficiency 18-2. 8 The expression of ectopic STXBP2 can cause an increase in the variability of the organs involved, making it very difficult to predict results. HSCT is the only curative choice for HLH patients with HLH-related gene mutations, nonresponse for primary therapy, or central nervous system involvement, but most patients will experience major treatment-related toxicity when transplanted after HLH is active. 4 It is important to note that no TRM in 16 AC transplanted before HLH development made this approach even more interesting.
The preemptive HSCT approach is currently favored in many other innate immune deficiencies with encouraging improvements. overall results. 4 Lucchini et al successfully demonstrated a clear increase in initial HSCT survival for patients with HLH while being asymptomatic. Brothers of HLH patients should be screened for specific mutations found in IC. If perforin mutations are found, the recommendation is to act temporarily asymptomatic for the possibility of achieving healing but if there are other mutations with a mild phenotype found, it might be reasonable to wait and watch. Hopefully, Lucchini et al will continue to collect cases and other centers will collaborate with them so that a stronger number of patients can be reported as validation of these initial results.
- © 2018 by The American Society of Hematology