A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Salvaged allogeneic hematopoietic stem cell transplantation for refractory/recurrent acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory/recurrent acute myeloid leukemia (AML).</p><p><b>METHODS</b>A total of 45 patients with refractory/recurrent AML were enrolled from September 2006 to April 2010. The median blasts in bone marrow (BM) were 36% (20% to 92%) before conditioning. The donors were identical siblings (6) or unrelated ones (9) or haploidentical family members (30). Conditioning regiments were individualized according to patients' status, the regimen with high-dose cytarabine plus BuCy/CY was mostly used (20). The patients with impaired organ function received above regimen except using fludarabine instead of cyclophosphamide (16). FLAG followed by reduced-intensified BuCy was employed for the recipients with more than 40% blasts in BM (6) to reduce leukemia burden. TBI/CY or TBI/Fludarabine was used for the recipients with extramedullary infiltration of leukemia or multidrug resistant leukemia. G-CSF, MTX, NVT, Vm26, Acla or Thaltipa was added into conditioning regiments according to leukemia character.</p><p><b>RESULTS</b>All but 2 patients attained durable engraftment. The incidence of grade II to IV aGVHD and cGVHD were 34%, 59.1%, respectively. With median follow-up 30 (0.5 - 57) months, the relapse rate was 29.2%. Twenty-nine of 45 (60.2%) patients remained in complete remission since salvaged HSCT. Three-years disease-free survival and overall survival were 60.2% and 62.6%, respectively.</p><p><b>CONCLUSION</b>Our results indicated that the combination of salvaged HSCT with prophylactic immunotherapy might be a promising modality for treatment of refractory/recurrent AML, even with high leukemia burden.</p>

Cytomegalovirus enteritis after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical features, diagnostic methods and risk factors of cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Analysis was made on 24 cases of CMV enteritis after allo-HSCT in Beijing Daopei Hospital from Aug. 2007 to Jul. 2009, including clinical data, endoscopic diagnosis, histopathological and virological results, and the association between CMV enteritis with viremia and graft-versus-host disease(GVHD).</p><p><b>RESULTS</b>87.5% of the patients were over 18 years old. The median time to diagnosis of CMV enteritis was 63 days after HSCT. The mucosal lesions in enteroscopic examination had no significant differences between CMV enteritis and gastrointestinal GVHD complicated with the enteritis. The methods used in diagnosis included histopathology (32.1%) and virology (92.9%). The copies of CMVDNA in mucosal samples greater than 10(5)/10(6) PBNC was better diagnosis. A number of risk factors were compared between the survival and death groups: type of transplant, conditioning regimen, the time span of ganciclovir prophylaxis therapy, grade II-IV GVHD before enteritis, the time of diagnosis as GVHD, using MP > or = 1 mg/kg to treat GVHD, the time between GVHD and enteritis, CMV viremia before enteritis, the time of diagnosis as enteritis, CMVDNA quantitation, and there were no any statistic differences.</p><p><b>CONCLUSION</b>Cytomegalovirus enteritis should be carefully diagnosed by histopathology and virology through endoscopic examination. It is better to undertake pan-colon endoscopy as well as terminal ileum examination for more accurate diagnosis. PCR can significantly improve the detection rate. CMVDNA detection in patients' stool may be helpful to diagnosis, especially for those patients who can not stand the endoscopy examination.</p>

The effect of inhibitory and activating natural killer cell immunoglobulin receptor on haplo-identical hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of inhibitory and activating KIRs on a cohort of Chinese leukemia patients who received haplo-identical hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Donor's inhibitory and activating KIRs and recipient's HLA-C from 47 cases who received haplo-identical HSCT were tested by PCR-SSP. 2 year overall survival (OS), incidence of severe (grade III to IV) acute GVHD (aGVHD) and relapse rate (RR) were analyzed.</p><p><b>RESULTS</b>(1) According to Matched (M) vs Mis-Matched (MM) between donor's inhibitory KIR and recipient's HLA-C1/C2 subgroup, 2 year OS rate in M group [(87.5 +/- 8.3)%] was significantly higher than that in MM group (54.5 +/- 9.0)%, (P = 0.03). Lower incidence of relapse rate was seen in M group than in M/MM groups [0 vs (25.4 +/- 9.5)%, P = 0.05]. In 30 cases of myeloid leukemia patients, there was lower RR in M group than in MM groups [0 vs (35.0 +/- 14.4)%, P = 0.04]. (2) According to the 3 activating KIR genes: KIR2DS1/ KIR2DS2/ KIR2DS3, lower incidence of grade III-IV aGVHD was seen in KIR2DS1 (+) group than in KIR2DS1 (-) group (13% vs 28%, respectively, P > 0.05); and so was done in KIR2DS3 (+) group (11% vs 26%, respectively, P > 0.05). The RR was lower in KIR2DS2 (+) group [0% vs (17.3 +/- 7.1)%, respectively, P > 0.05].</p><p><b>CONCLUSIONS</b>In our haplo-identical HSCT setting, match between donor's inhibitory KIR and recipient's HLA-C can significantly reduce the incidence of relapse rate and improve OS. Although lower incidences of severe aGVHD are noted in the donors with KIR2DS1 (+) or KIR2DS3 (+), and lower relapse rate is noted in the donors with KIR2DS2 (+) but without statistic difference, no remarkable effects of activating KIRs on OS have been found in our relatively small clinical series.</p>

Influence of HLA-A/B/C/DRB1/DQB1 on unrelated donor hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to explore the influence of number and locus of HLA allele mismatch on unrelated donor hematopoietic stem cell transplantation (URHSCT) in Chinese Han population. Total 10 alleles within the HLA-A/B/C/DRB1/DQB1 loci were analyzed by PCR-SSP for 101 pairs of donor and recipients who received URHSCT. 101 cases of URHSCT were divided into four groups: HLA-allele 10/10 match (n = 30), 9/10 (n = 32), 8/10 (n = 31) and 7/10 match (n = 8). The correlation of the HLA with overall survival (OS ≥ 1 year), incidence of acute GVHD (aGVHD) of grade II to IV and relapse rate of primary diseases were evaluated. The results showed that (1) The OS rates in HLA-10/10 and 9/10 groups were higher than that in HLA-8/10 match group (78% and 82% vs 50%, p = 0.39); incidence of aGVHD in the HLA-10/10 were lower than that in HLA-9/10 and HLA-8/10 group (0% vs 10% and 10%; p = 0.28); relapse rates among the 3 groups were close (16%, 18% and 20%, respectively). Although there were only 8 cases in HLA-7/10 match URHSCT, the data indicated that they were safe and effective; (2) Compared to the HLA-10/10 match URHSCT (n = 30), the HLA-C mismatch URHSCT (n = 12) harbored higher incidence of severe aGVHD (0% vs 25%, p = 0.006), longer OS (77% vs 85%, p = 0.30), and tendency to low relapse rate (8% vs17%, p = 0.47); (3) According to HLA-C1/C2, the ligands of inhibitory KIR, the 42 cases of HLA-10/10 match URHSCT and HLA-C mismatch URHSCT were grouped into donor/recipient HLA-C1/C2 match and mis-match subgroups. There was no difference between the two subgroups for OS, incidence of aGVHD and relapse rate (78% vs 80%, 14% vs 20%, and 5% vs 20%). It is concluded that for 0 to 2 locus of HLA allele mismatch in URHSCT, the fewer mismatch numbers, the longer OS, but with similar aGVHD incidence and the relapse rate; triple HLA allele mismatch (HLA-7/10 match) is safe in URHSCT. The HLA-C mismatch may be related to higher incidence of aGVHD and lower relapse rate and prolonged OS, remaining to be further studied.

Role of HLA protein three-dimensional conformation difference in unrelated hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to investigate the value of Histocheck and HLA-Matchmaker softwares in evaluating influence of HLA protein three dimensional conformation among individuals on outcome of unrelated donor hematopoietic stem cell transplantation (URHSCT). Data of the HLA-A/B/C/DRB1/DQB1 genotypes from 62 cases of URHSCT (HLA-allele 10/10 match 30 cases, 9/10 match 32 cases) were input into Histocheck and HLA-Matchmaker softwares respectively. The relationship between the software dissimilar scores and the 1 year overall survival (OS), incidence of aGVHD of III-IV grade and relapse rate was analyzed. The results showed that (1) with increase of the Histocheck scores, incidence of aGVHD of III-IV increased from 0% to 20% (p = 0.25), while no or mild aGVHD occurred in 70% cases with the high scores. For the relapsed cases, there was no significant difference between the cases with low scores and with highest scores (relapse rate 20%) except that 9 cases had no relapse in the group with higher score (11 - 20). (2) the analysis using HLA matchmaker software showed that incidence of aGVHD of III-IV grade increased with the increase of numbers of mismatch Eplets, arranging from 0% to 30%, the incidence of moderate aGVHD reduced (p = 0.019), whereas 60% cases in highest scores group had moderate aGVHD. No relapse occurred in the group with higher scores (≥ 3) (n = 10), whereas high relapse rate appeared in the lower score group (20%, p = 0.54). It is concluded that the value of Histocheck and HLA-Mtchmaker software for analysing the outcome of URHSCT may be similar despite of different calculating methods; for the certain pair of recipient and donor, correlation of the two score systems with incidence of aGVHD and relapse rate is similar, but with less accuracy; The HLA Matchmaker software appears better than Histocheck software in terms of correlation.

Diagnostic value of plasma (1, 3)-beta-D glucan assay for invasive fungal infections in patients with hematological disorders / 中国实验血液学杂志

The invasive fungal infections (IFI) in immunocompromised patients are associated with a high mortality rate and diagnostic difficulty. Serological methods such as aspergillus galactomannan assay (GM test) and (1, 3)-beta-D glucan (BG) assay (G test) can be used as an adjunctive method for IFI diagnosis based on their characteristics of easy-operating, rapidness and high sensitivity. Compared with GM test, G test can be more widely used except for the diagnosis of aspergillosis. The purpose of this study was to investigate the value of G test in the diagnosis of IFI in patients with hematological disorders. The plasma was collected from 162 suspected IFI patients with hematological disorders in Beijing Daopei Hospital, including 85 patients after chemotherapy and 77 patients after stem cell transplantation from May 2007 to May 2008, BG level was measured with MB-80 Microbiology Kinetic Rapid Reader and the measured results together with the clinical characteristics were retrospectively analyzed. According to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, there were 2 patients diagnosed as proven IFI, 18 as probable IFI, 75 as possible IFI and 67 as no IFI. The results showed that at a cutoff of 20 pg/ml, the sensitivity and specificity of G test were 75% and 91% respectively, with a positive predictive value (PPV) of 71.4% and a negative predictive value (NPV) of 92.4%. 51 out of the 75 possible IFI patients with elevated BG level were responsive to antifungal treatment but non responsive to broad-spectrum antibiotics, retrospectively were diagnosed as IFI, suggesting that G test improved the IFI diagnostic rate by 31.4%. In conclusion, G test is a rapid and simple method for early diagnosis of IFI in patients with hematological disorders.