Tisitabin United Semi-Compatible Lymphocyte Infusion Treatment MDS Allogeneic Hematopoietic Stem Cell Transplant progresses into AML and multiple recurrences 1 case

Ishee-based hematotransplantation (allogeneic stem cellation, allo-HCT) is considered the only option for treating myelodysplastic syn -drome, MDS? However, relapse is the main reason for the failure of HCT treatment, Molina and other (1) in a retrospective analysis of HCT recurrence rate of 31% , 54 months after recurrence total survival rate of 45% , 4% ?1 case datapatients, male, 46 years old, in August 1998 no obvious cause of fever, body temperature of 42.0 degrees C, with fear of cold? Chills? Palpitations? Chest tightness? Breath? Weak? Blood routine: WBC 2.56 x 10 9/L, HGB 80g/L, RBC 2.6 x 1012/L, PLT 70 x 10 9/L? bone marrow like: bone marrow hyperplinter, granulation: red s0.61, granulation reduction reduced, raw granule scarcity 1.5%, red family hyperactive? Chromosome nucleotype is 46, XY ,diagnosticmDS - RAEB? Give standard DA regimen (juric and tymcine 60mg d1 to 3 plus aglycosine 2.0g d1 to 7) 1 cycle up to complete remission (CR), consolidate 6 cycles of therapy, period bone marrow image is all up to CR, in April 1999 full-
Stem celltransplant, in November 2011 bone marrow show bone marrow growth life leap, raw granulocytes accounted for 24.5%? Flow cytokine test: infant cell accounted for 65.0%, CD13 plus cell 18%, CD33 plus cell 92.0%, CD14 plus cell 2%, HLA-DR plus cell 3.5%, CD117 plus cell 18%, T cell? B-cell antigens are negative? Color body core type: 46, XY s.20, fusion base detection WT1/ABL s 0.09? FLT3 - ITD/TKD? Npm? c -kit are negative, inlay 89%? Diagnosed as AML-M2, given standard programmed therapy combined with compatriots all-in-combination lymphocyte infusion treatment after remission, February 2012? In March, 1 cycle of standard programmed combination and cytosic lymphocyte infusion consolidation therapy was given, 2 cycles of fully compatible lymphocyte infusion consolidation therapy were given in April 2012, treatment was discontinued from May 2012 to 2017, and regular re-examination was made, Bone marrow like CR, chimeric is greater than 95%, during which patients suffer from skin chronic transplantation anti-host disease (cGVHD), performance of scleronosis: limb skin mucosal epidural, associated joint activity is limited, given oral cyclosporine therapy, poor results? March 2018 22 review, bone marrow show: bone marrow hyperplinter active, raw granulocytes accounted for 22.0%, early granulocytes accounted for 24.0%, leukemia residual scan: CD34 (s) CD117 (plus) CD13 (s) CD33 (and) CD33 ()CD33 ()CD7 HLA-DR (-) CD38 (-) CD15 (-) CD64 (-) CD19 (-) CD56 (-) CD45 (dim) Abnormal myelin original cell accounted for 7.26%, 43 fusion base Due toscreeningnegative, 42 myelin gene mutations prompt TET2 mutation, disease recurrence, but the patient's skin still has cGVHD, then tried to give the daughter to mobilize after the semi-phasely lymphatic cell infusion combination treatment, specific treatment see table 1, now stop treatment for more than 1 year, bone marrow like STILL CR, white blood disease residual negative2 Discussioncurrently for allo-HCT after the recurrence of disease, has been tried including palliative care, discontinuation ofimmuno
inhibitors, azacytosine, donor lymphocyte infusion (DLI), secondary HCT, tyrosine kinase inhibitors, cell immunotherapy and other methods as a cure, but for allo-HCT after the recurrence of patients still do not have a standard treatment? DLI is a recognized treatment option for recurrent diseases of the disease after a blood or bone marrow transplant of a compatriot or non-blood-related donor (MUD) of HLA match, but there are still few reports of semi-compatible lymphocyte infusions, Zeidan et al-HCT recurrence Patients with semi-compatible lymphatic cell therapy results, of which 12 (30%) patients responded to semi-compatible lymphocyte infusion therapy, up to CR, median reaction duration of 11.8 months (average 22.5 months) Range 0.4 to 94.0 months), only 10 (25%) patients with aGVHD, and 2 of which died in aGVHD patients (both III-degree GVHD)? The reasonable initial dose of lymphocytes, the CR rate of patients under this dose was 26.7%, and only 16.7% of patients had II-IV-degree GVHD, semi-compatible lymphatic cell infusion treatment of allo-HCT recurrent disease Is it feasible, sustained reaction can be achieved, and toxicity is within acceptable limits? However, the sample size is small, the relevant literature is lacking, still need forward-looking assessment to confirm the role and toxicity of semi-compatible lymphocytes? DLI has anti-white blood disease effect, however, due to the injection of gonorrhea cells reduced or due to the increasing burden of leukemia cells, this treatment effect usually only lasts 3 to 4 months, in order to improve the prognosis, DLI can be combined with chemotherapy drugs application? Demethylation drugs, including dixibin and asocytine, can inhibit DNA methylation transenzyme, causing DNA low methylation, thus playing an anti-tumor and regulating immune and other effects? Related studies have shown that tisitamon combined chemotherapy shows better therapeutic results in patients with relapse in refractive aML? A study that successfully controlled the early recurrence of leukemia in a patient with 1 MDS-converted AML patient using the DLI of the west-thyaben joint DLI successfully controlled the patient's early recurrence, making it a good long-term no-progress survival? The International Panel of Experts suggested that patients with relapse after MDS HCT, with DLI, could extend the life of eventless patients by 15% to 31%, while patients with AML patients with Combined Treatment of DLI and Azacytosin relapse after HCT with MDS-related changes In, 28 patients with relapses had a 2-year survival rate of 66% to 10%? A study table, adsacyscosides have the ability to reduce the risk of recurrence on tumor antigen CD8 (-) T cell response patients, HCT after each month to take adsacyscosides can make non-recurrence survival rate improved? A study by Schroeder et al(7) analyzed the combination of dissyertine and DLI as a remediation of relapse after allo-HCT, which collected 36 patients with relapse, 29 cases of AML, 7 cases of MDS, and the median western of the patients The number of dLI cycles in his bin is 2 (range 1 to 11)? Of these, 16 cases (44%) of ditisabin as the first patient after recurrence, and 20 (56%) patients who have previously received 1 to 5 other treatments? Results, the total body reaction rate of 25%, including 6 cases (17%) CR and 3 cases (8%) partial remission, 6 cases of CR patients did not relapse, CR's median survival period of 10 months (range of 2 to 33 months), which indicates that the tithobin joint DLI treatment allo -HCT is feasible, can also be used as a second-line treatment after the failure of first-line treatment? Sommer et al (8) also proved that the ground-west-tametin united DLI program is feasible and effective in allo-HCT post-recurrent myelinous tumor? In the past, it has been shown that t-cell (Tregs) plays a protective role in the disease-producing system of cGVHD, and the low methylation of the transcriptional Foxp3 gene is the key to determining Treg's function? Studies have shown that DNA methyl transferase inhibitors such as asonucleoside? Can the geo-pacifician make the Foxp3CNS2 region and Foxp3 enhanced sub-methylation to induce Foxp3 expression in vivo and in vitro, and the use of low-methylation agents can reduce the effects of transplant resistance to host disease without sacrificing the effects of graft seroidal leukemia? Fransolet et al (10) with mouse modeling experiments, proved that the demethylation drug azacytosinin in the establishment of good mouse models prevention scleronoscindisease cGVHD? In addition, demethylation drugs have anti-tumor active action, has been recognized as its anti-tumor active mechanism is to reactivate the abnormal lysamic inhibition of tumor semaphore, DNA repair base and microRNA (11?) Geosythabin therapy also led to an increase in tumor antigens, such as melanin cancer-related antigen 1 (MAGE1) and testicular cancer antigen (CTA) (12)? Recently, studies have shown that demethylation drugs can raise endogenous retrovirus (ERV) transcripts, which form fine cytoplasmic double-stranded RNA and cause apoptosis (13-14), and CTA, ERV is likely to increase immunogenic cancerous cells, thus making immune treatments such as PD - 1, DLI more susceptible (13-15)? This example MDS -RAEB patients, after 6 cycles of standard treatment, bone marrow like CR, chromosomes for normal nuclear type, allo -HCT, transplant process smooth, regular follow-up are in CR, insert syllin is greater than 95 %?12 years after transplant review of bone marrow like: increase dyseosetle, raw granulocytes accounted for 23.5%, early granulocytes accounted for 0.5%, diagnosis for AML, after multi-cycle standard program joint brother DLI treatment, bone wear up to CR, embedded The combination is greater than 95%? Stop treatment for 6 years, regular review, bone wear is up to CR, the disease did not progress, during the skin cGVHD, oral cyclosporine treatment poor efficacy? 6 years later relapse, give standard program after treatment relief, but Considering that the patient's skin has chronic rejection, still re-emerged, and then the second infusion cell brother all-in-one DLI effect may not be good, then try to combine the daughter after the mobilization of semi-phasely lymphocyte therapy, another primary disease is MDS, and the combined TET2 mutation? Scleronopathy, given to the sitabin joint semi-compatible lymphnode cell infusion maintenance treatment 3 cycles, during the review of bone wear is up to CR, and the skin cGVHD gradually reduced? Has stopped treatment for 1 year, regular review, bone marrow like still in CR, flow inglisile residual lesions negative? Analysis of the patient's condition, for allo-HCT after relapse patients, its tumor load is large, relying solely on DLI-induced graft anti-white blood disease effect can not make myelodonido cr, can be combined standard protocol-induced CR to reduce the tumor load? For patients with rejection and bone marrow recurrence, semi-compatible lymphatic cell infusion can be used as an alternative, while joint demethylation drug dixibin strengthens anti-tumor activity and makes tumor cells more susceptible to DLI, while inducing Foxp3 boosters to demethylate, strengthening the anti-GVHD effect of Treg cells, toxicity is relatively small? However, the dose selection of infusion semi-combined lymphnode cells? The cycle required to maintain treatment? Maintenance of post-treatment survival time and other issues need forward-looking research proof? References?