Refractory High-Risk Organ Involvement
A new treatment plan is indicated when a patient with multisystem involvement shows progressive disease after 6 weeks of standard treatment, or has not had a partial response by 12 weeks. Data from the DAL Group studies have shown that these children have only a 10% chance of surviving. Results from the LCH-II trial revealed that patients treated with vinblastine/prednisone who did not respond well by 6 weeks had a 27% chance of survival, compared with 52% for good responders.[Level of evidence: 1iiA] All studies suggest that patients with poorly responsive disease need to be changed early to salvage strategies at 6 weeks for progressive disease and no later than 12 weeks for those without at least a good response.
Cladribine and 2'-deoxycoformycin have been tested as salvage therapies for LCH.[11,15]; [Level of evidence: 3iiiDiv] A case series reported that patients with multiple reactivations or high-risk disease could be effectively treated with continuous-infusion cladribine for 3 days. Seven of ten patients on this trial required no more therapy.[Level of evidence: 3iiiDii]
Patients with refractory high-risk organ (liver, spleen, or bone marrow) involvement and resistant multisystem low-risk organ involvement have been treated with an intensive acute myeloid leukemia-like protocol. Prompt change of therapy to cladribine and cytosine arabinoside appeared to provide an improvement in overall survival (OS).; [Level of evidence: 3iiiDii]; [Level of evidence: 3iiiDiv] This is a very intense regimen and requires that physicians are able to treat infectious and metabolic complications. Responses may be delayed.
Six patients with multiorgan LCH resistant to other agents, including cladribine, were reported to respond to treatment with clofarabine.; [Level of evidence: 3iiiDii] An additional 11 patients with recurrent multisystem high-risk and low-risk disease had a 90% OS. If confirmed in prospective trials, the reduced toxicity of this regimen, compared with the cladribine/cytarabine combination, could be advantageous despite the cost of the drug.
Hematopoietic stem cell transplantation (HSCT) has been used in patients with multisystem high-risk organ involvement that is refractory to chemotherapy.[7,23,24,25] The use of reduced-intensity conditioning, especially for patients that have received intensive chemotherapy just before HSCT, may reduce toxic deaths and improve outcome.