Comparison of rabbit ATLG and ATG for GVHD prophylaxis in hematological malignancies with haploidentical hematopoietic stem cell transplantation.

Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT). Yet, their efficacy and safety have seldom been compared in hematological malignancies with haploidentical HSCT. A retrospective analysis with 28 ATLG (total dosage, 20-30 mg/kg) and 18 ATG (total dosage, 8-10 mg/kg) patients were performed. The cumulative incidences of chronic GVHD and relapse were comparable between both groups. ATLG showed a trend towards a lower acute GVHD incidence (28.6% vs. 44.4%, P = 0.242) and 3-year non-relapse mortality (10.7% vs. 27.8%, P = 0.160), and had a significantly higher 3-year overall survival (OS, 64.3% vs. 33.3%, P = 0.033) and GVHD-free and relapse-free survival (GRFS, 32.1% vs. 11.1%, P = 0.045) compared with ATG. Multivariate Cox regression analysis demonstrated ATLG was independently associated with a favorable OS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.16-0.86, P = 0.020) and GRFS (HR = 0.51, 95%CI: 0.26-1.00, P = 0.051). Furthermore, ATLG had a lower risk of fever (25.0% vs. 61.1%, P = 0.014) and hemorrhage cystitis (7.1% vs. 38.9%, P = 0.008) than ATG-T. In conclusion, ATLG confers more survival benefit and a better safety profile than ATG and can be used in hematological malignancies with haploidentical HSCT. Prospective designed trials with a larger sample size are warranted to confirm the results in the future.

Post-transplant cyclophosphamide for GVHD prophylaxis in pediatrics with chronic active Epstein-Barr virus infection after haplo-HSCT.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a rare but life-threatening progressive disease. Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the best choice as sometimes HLA-matched donor is not accessible. However, graft-versus-host-disease (GVHD) following transplantation remains a major cause of treatment failure and elevated mortality. Post-transplant cyclophosphamide (PTCy) has recently emerged for effective GVHD prophylaxis in a haploidentical setting in many hematologic malignancies. Here, we report the performance of PTCy for GVHD prophylaxis in a series of CEABV patients treated with haplo-HSCT. METHODS: Consecutive pediatric CAEBV patients who were treated with haplo-HSCT and give PTCy for GVHD prophylaxis were analyzed. 1-year GVHD and relapse-free survival (GRFS), overall survival (OS) and cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) were estimated. RESULTS: A total of 8 patients ranging from 2 to 15 years old were included. Among them, 4 patients had early complications after haplo-HSCT. Counts of T-cell subsets increased within 6 months post transplantation, indicating an immune reconstitution. Only 1 patient developed grade II acute GVHD, and 2 patients had moderate cGVHD. One patient died from diffuse alveolar hemorrhage within the first year after transplantation. The 1-year GRFS rate, OS rate and cumulative incidence of moderate-to-severe cGVHD were 62.5%, 87.5% and 25.0%, respectively. CONCLUSION: Our findings suggest that, among CAEBV patients treated with haplo-HSCT, PTCy may be an alternative choice for the prevention of GVHD.

A new intensive conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with refractory or relapsed acute myeloid leukemia.

To explore the efficacy, and safety of the intensive conditioning regimen consisting of cladribine, cytarabine (Ara-C), and granulocyte colony-stimulating factor (G-CSF) plus modified busulfan (Bu) combined with cytoxan (Cy) (BuCy), prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory, or relapsed acute myeloid leukemia (R/R AML).Thirty-Six R/R AML patients scheduled to receive allo-HSCT were consecutively, enrolled in this prospective study, and treated using intensive conditioning regimen consisting of CLAG plus modified BuCy. Median follow-up duration was 11.25 (range 0.5 - 21.0) months and the last follow up date was August 15, 2017.All patients (100%) achieved white blood cell (WBC) recovery within a median time of 16.00 (13.25 - 18.00) days, and 34 of them (94%) attained platelet (PLT) recovery within a median time of 13.50 (9.25 - 19.75) days. Incidence of acute graft-versus-host disease (aGVHD) was 50.00%, with median time of 71.50 (41.00 - 401.25) days. Three patients developed Grade I; nine, Grade II; 5, Grade III; and 1, Grade IV aGVHD. The incidence of chronic GVHD (cGVHD) was 44.40%, with median time of 255.00 (120.00 - 390.00) days. Four patients developed limited cGVHD, and 12, extensive cGVHD. One-year accumulating leukemia free survival (LFS), and overall survival (OS) rates between 52.9 ±â€Š8.8% to 69.4 ±â€Š7.7%, respectively. Eighteen (50%) patients were infected with cytomegalovirus; 2 (5.6%), with Epstein-Barr virus (EBV), 7 (19.4%), with hemorrhagic cystitis; 13 (36.1%), with bacteria; and 8 (22.2%), with fungus.Intensive conditioning regimen of CLAG plus modified BuCy for allo-HSCT may be effective and well-tolerated in R/R AML patients.

[Changes of cell immunophenotypes after transformation from myeloproliferative disorders into acute myeloid leukemia].

Some cases of myeloproliferative disorders (MPD) could be transformed into acute myeloid leukemia (AML), but the cell differentiation process of MPD into AML has not yet been observed in vivo. This study was aimed to reveal this differentiation process. The flow cytometry was used to analyse the immunophenotype of differentiated cells of 2 MPD cases who developed into AML in a short time. The reports showed that the different MPD-AML subclones are presented when the MPD cells that proliferate slowly in vivo become the AML blast cells that proliferate rapidly. It is concluded that understanding the process of MPD crisis will help the MPD-AML early diagnosis and treatment.

[Relationship between V617F mutation and 46/1 haplotype in JAK2 gene in patients with chronic myeloproliferative diseases and frequencies of 46/1 haplotype in different Chinese nationalities].

Somatic gene V617F mutation in JAK2 is a critical molecular and biological indicator to diagnosis of chronic myeloproliferative disease (MPD). This study was aimed to investigate the genetic background of V617F mutation in 46/1 gene haplotype in Chinese MPD patients, and the frequencies of 46/1 gene haplotype and V617F mutation in three nationalities of Chinese populations. Peripheral blood or bone marrow samples of 150 V617F mutation positive MPD patients, 123 V617F mutation negative MPD patients, 124 healthy Han individuals, 395 healthy Tibetan individuals and 315 healthy Yugu individuals were collected. The allele-specific multiplex PCR method was established, the presence or absence of V617F mutation, the presence or absence of 46/1 haplotype, and the relationship between V617F and 46/1 haplotype were easily identified by agarose gel image. The results showed that the V617F mutation located in the 46/1 haplotype of 88 cases (58.67) among 150 V617F-positive MPD cases. In 814 Chinese healthy individuals including Han, Tibetan, Yugu nationalities, the frequency of the 46/1 gene haplotype was 38.37 without difference in the frequency among different nationalities, and no V617F mutation was found in Chinese healthy populations, The frequency of the 46/1 gene haplotype was 43.09 in V617F mutation negative MPD patients and was 69.33 in V617F mutation positive MPD patients, the latter was obviously higher than former and than that in healthy Han individuals. In conclusion, a multiplex PCR method has been developed that is simple and useful to identify V617F mutation in JAK2 gene and its relationship to the 46/1 haplotype. In more than half of Chinese V617F-positive MPD patients, the V617F mutation locates in 46/1 haplotype in JAK2. The frequencies of 46/1 haplotype are statistically insignificant among Han, Tibetan and Yugu nationality populations.

[Immunogenetic diagnosis of large granular lymphocytic leukemia and therapy by sirolimus].

This study was aimed to investigate the immunogenetic diagnosis of large granular lymphocytic leukemia (LGLL) and therapeutic efficacy of sirolimus, and to analysis 256 cases of LGLL reported at home and abroad within 2000 - 2010. Besides the routine examination of peripheral blood and classification of bone marrow cell morphology, the expression of T cell receptor variable region of ß-chain (TCR BV), CD3, CD4 and CD8, as well as TCRαß, TCRγδ were detected by flow cytometry; the RT-PCR was used to amplify and determine the TCR gene spectrotypes, and to analyze the clonality of abnormal cells. Sirolimus was first given to patients who did not gain efficacy from common agents. The results showed that lymphocytosis happened in all LGLL patients, but patients from West countries always displayed neutropenia while Chinese patients always displayed anemia. In 2 out of 4 patients from our hospital, the large granular lymphocytes (LGL) were difficult to be distinguished. In all 4 patients, almost all lymphocytes were CD3(+), CD8(+), and TCRα/ß(+). TCR BV 24 gene family clones showed monoclonal TRBV 23, TRBV 20, TRBV 13.6, and TRBV 13.6, respectively. FCM results were consistent with those of RT-PCR. When 4 patients had been given sirolimus (6 mg first dose, 2 mg once a day) for about 1 week, hemoglobin level and reticulocyte count increased significantly without any serious side effects. It is concluded that the detection of specific lymphocyte monoclonal TCR BV 24 gene family by FCM contributes to the diagnosis of LGLL. Sirolimus is an effective agent without serious side effect for LGLL patients, especially for patients who cannot tolerate common drugs.