MCP-1 and VCAM-1 As Pathological Markers In a Patient With Infection Induced Hemophagocytic Syndrome After Stem Cell Transplantation
Authors: Hayashi Kunio , Ikegame Kazuhiro , Ito Masafumi , Nomura Shosaku 
Published: October 2019

Abstract
The origin of macrophage in HPS after SCT was also very interesting to be examined.

Material and Method
The characteristics of the patients and the information of infections were summarized in Table 1.
1. IL6, MCP|1, VCAM-1, TNF-a, RANTES, sE-selectin and HMGB1were measured by immunosorbent assay of cryopreserved blood samples.
2. In situ hybridization was performed to paraffin sections of aspirated bone marrow cells whose sex chromosome were dyed in different colors to detect the Y chromosome in macrophages.
Result yperferritinemia and high levels of serum soluble interleukin-2 receptor were recognized. On day14, initial neutrophil engraftment and complete chimerism were successfully achieved. High dose mPSL 1000mg/day was administered several times but phagocytosis was little better and finally peripheral bloods were completely deprived (secondary graft failure). About sex chromosome, mononuclear cells had XX (donor type) but the phagocytes held original chromosome XY (recipient type). MCP-1 and VCAM-1 were rising up steadily but another adhesion molecule E-selectin or cytokines were not elevated (Fig1.). The same movement of MCP-1 and VCAM-1 was recognized in the case of patient#4 EBV-associated HPS who had immunological dysfunction with Bechet disease. The following two cases, patient #2 and #3 who received haplo-mini-SCT showed completely different cytokine movement. Patient #3 who was 75y.o.female with AM/MDS was infected with multiple candida species after haplo-mini-transplantation. MPC-1 inversely decreased less than 400 pg/ml. Patient#2 who was 60y.o. female with AML(M1) de Montréal (CHUM) between June 1, 2012 and May 31, 2013. Date was collected through medical and pharmaceutical patient records. Our local ethics board approved this study.

Results
A total of 45 patients received bortezomib for MM or amyloidosis with a median age of 68 years (SD ± 9.3) and 53.3 % were male. Patients received bortezomib in various protocols including Vel-Dex (42.2%), VMP (44.4%) and CyBorD (13.3%). The median starting dose of bortezomib was 1.3 mg/m2 (SD ± 0.13). Patients received SC only bortezomib injections (71.1%) or IV only (15.6%) or were switched from IV to SC (13.3%) for a total of 157 cycles (786 doses). A total of 444 BP values before and 425 BP values after SC bortezomib were analysed. No significant difference was detected between the average systolic BP (125 vs 125; p=0.76), diastolic BP (70 vs 71; p=0.77) or heart rate (79 vs 78; p=0.89) between the 2 measurements. Hypotension, defined as a drop of 20 mmHg of systolic BP, occurred 18 times (4.2%) but systolic BP was never below 90 mmHg. One patient had a severe dysautomia, possibly related to bortezomib that required the discontinuation of the treatment. At our center, CBC are performed prior to each bortezomib dose. Neutropenia occurred in 10 % of the total doses received. Risk factors influencing neutropenia were the use of oral alkylating agent (melphalan and cyclophosphamide) in the regimen and baseline neutrophil count less than 2.0 x 109. Many patients also received bortezomib for a relapsed / refractory disease and were previously exposed to many lines of therapy. Thrombocytopenia occurred in 7,2% of doses received. Cutaneous toxicity occurred mostly with the first patients treated with the SC technique. With time, nursing changed their technique and further skin reactions were less reported. Neuropathy occurred in 21 patients (13 SC, 4 IV, 4 IV to SC), caused dose reductions in 7 patients (2 SC, 2 IV, 3 IV to SC) and treatment discontinuation in 2 patients (SC).

Conclusion
Our results demonstrate SC bortezomib was well tolerated. The rates of hypotension was quite low. Also rates and intensity of neutropenia and thrombocytopenia varied among different bortezomib containing regimens. Because of the low rate of profound neutropenia, Vel-Dex and VMP protocols can be modified to decrease the number of CBC to once weekly during the cycle rather than before every injection. More data are needed with CyBorD protocol before drawing any conclusions.

Disclosures:
Adam: Jansen Ortho: Honoraria. Lemieux-Blanchard: Celgene: Honoraria. Lemieux: Jansen Ortho: Honoraria.