The haploimmunostorm syndrome: A distinct clinical entity seen in HLA-haploidentical cellular immunotherapy
Year: 2006
Type: article
Study design: Clinical Trial
Abstract: An immune-mediated anti-tumor response is the ultimate goal of allogeneic transplantation for relapsed, refractory malignancies. We developed a transplant protocol with less toxicity compared with standard allogeneic transplantation. We utilized multiple donor lymphocyte infusions after nonmyeloablative HLA-haploidentical stem cell transplantation for refractory disease. We have performed a total of 41 HLA-mismatched transplants with escalation of the CD3+ dose to 2 × 108 cells/kg using G-CSF primed product, with a conditioning regimen of 100 cGy total body irradiation. Our phase I/II study had 26 with hematologic malignancies. This therapy results in loss of detectable macrochimerism. Despite this, 13 responses, six major, occurred outside of macrochimerism. We have observed a new infusion related clinical entity named haploimmunostorm (HIS), observed after infusion. This syndrome occurred in 26 out of 30 (87%) patients with a CD3+ dose more than 1 × 108 cells/kg. In the syndrome, a constellation of symptoms occurred, some with variable penetrance, in which hyperpyrexia and malaise were a constant feature occurring as early as 4 hrs after cell infusion (median of 14 hrs). A morbilliform rash was seen in 40% of patients. Biopsies revealed no evidence of hyperacute or acute GVHD. Diarrhea was present in a 20% of patients; biopsies taken also failed to show any evidence of GVHD. Transient elevations of liver enzymes occurred in 40% of the patients usually. Steroids were used successfully if the HIS syndrome lasted more than 72 hrs. We used a Bioplex machine and analyzed 17 separate cytokine levels serially in these patients beginning with pre-treatment levels. Cytokine level analysis showed up to a 90 fold increase in baseline cytokine levels with significant increases of at least 10 fold in IFN-γ, IL-10, IL-13, IL-2, IL-5, IL-6, IL-7, IL-8, MCP-1, and MIP-1β. This syndrome appears to be immunologically based and represents neither hyperacute nor acute GVHD. This syndrome is different than an engraftment syndrome reported in some patients undergoing autologous transplant. Engraftment syndrome occurs at time of engraftment, opposed to HIS in which may be a rejection syndrome. Engraftment syndrome is similar to HIS but deviates with presence of capillary leak and pulmonary infiltrates. In summary, we have observed a new clinical entity that was not previously seen and is a result of the donors having a relatively intact immune system at the time of cell infusion.
Institutions: Roger Williams Medical Center, Massachusetts General Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2040891357