Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.

BACKGROUND AIMS: The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown. METHODS: In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively. RESULTS: The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders). CONCLUSIONS: For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.

Circ_0009910 shuttled by exosomes regulates proliferation, cell cycle and apoptosis of acute myeloid leukemia cells by regulating miR-5195-3p/GRB10 axis.

The exosomes are involved in intercellular communication via RNA trafficking in human diseases. Hsa_circ_0009910 (circ_0009910) is a novel leukemia-related circular RNA. However, the mechanism of circ_0009910 in acute myeloid leukemia (AML) cell-to-cell communication remained obscure. Expression of circ_0009910, miRNA (miR)-5195-3p and growth factor receptor-bound protein 10 (GRB10) was detected by quantitative real-time polymerase chain reaction and Western blotting. A stable cell coculture model was established and functional experiment was performed using Cell Counting Kit-8 assay, flow cytometry, and Western blotting. The interaction among circ_0009910, miR-5195-3p and GRB10 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. As a result, circ_0009910 was upregulated in AML bone marrows and cells (HL-60 and MOLM-13), even higher in AML cells-derived exosomes. Functionally, blocking circ_0009910 via small interfering RNA (siRNA) suppressed cell proliferation and cell cycle progression, but facilitated apoptosis rate of HL-60 and MOLM-13 cells, accompanied with lower B-cell lymphoma 2 (Bcl-2) level and higher Bcl-2-associated X protein (Bax) level. circ_0009910 shuttled via exosomes negatively regulated miR-5195-3p expression by target binding. Furthermore, circ_0009910 knockdown via exosomes and miR-5195-3p overexpression via mimic resulted in similar results of circ_0009910 siRNA in proliferation, apoptosis and cell cycle progression of AML cells. Meanwhile, the role of circ_0009910 knockdown in AML cells was partially reversed by miR-5195-3p deletion, and restoring GRB10 could abrogate miR-5195-3p effect as well. Notably, GRB10 was a downstream target of miR-5195-3p. circ_0009910-containing exosomes mediated proliferation, apoptosis and cell cycle progression of AML cells partially through miR-5195-3p/GRB10 axis.

Outcomes of allogeneic haematopoietic stem cell transplantation for patients with severe aplastic anaemia using the porcine antilymphocyte globulin-containing conditioning regimen.

Antithymocyte globulin (ATG) is widely used for allogeneic haematopoietic stem cell transplantation (allo-HSCT) in severe aplastic anaemia (SAA). Only rabbit-ATG (r-ATG) and porcine-antilymphocyte globulin (p-ALG) are available in China, but the p-ALG-containing conditioning regimen for allo-HSCT in SAA has seldom been reported. In this study, we retrospectively evaluated the outcomes of 41 SAA patients receiving allo-HSCT with a p-ALG-containing conditioning regimen in our transplantation centre. All patients engrafted, and no death during conditioning was observed. The actuarial 3-year overall survival (OS) rates were 95.1 ± 3.4%. The actuarial 3-year disease-free survival (DFS) rates were 85.0 ± 5.7%. Acute graft-versus-host disease (aGVHD) predicted inferior OS (p < 0.05). The interval from diagnosis to transplantation for more than 100 days predicted an inferior DFS rate (p < 0.05) and a higher graft rejection/poor graft function (GR/PGF) rate (p < 0.01). In conclusion, the p-ALG-containing regimen showed satisfactory effects and safety in allo-HSCT for SAA patients. P-ALG could be a potential alternative preparation for r-ATG in SAA allo-HSCT.

Allogeneic stem-cell transplantation for peripheral T-cell lymphoma: a systemic review and meta-analysis.

Peripheral T-cell lymphoma (PTCL) comprises a heterogeneous group of mature T-cell tumors with a poor prognosis; allogeneic stem cell transplantation (allo-SCT) may offer a potential way of cure for these patients though the optimal type and timing of transplantation remain to be defined. We performed a systemic review and meta-analysis examining the efficacy and safety of allo-SCT for PTCL. The pooled 3-year overall survival (OS) of PTCL patients treated with allo-SCT was 49.6% (95% confidence interval, CI: 41.7-57.5%). A meta-analysis of 3-year OS in allo-SCT and autologous SCT (auto-SCT) showed no statistical difference. The rates of pooled acute graft-versus-host disease (GVHD; grade 2/4) and chronic GVHD were 26.7% (95% CI: 21.4-32.9%) and 29.9% (95% CI: 24.3-36.1%), respectively. The pooled 100-day treatment-related mortality was 24.2% (95% CI: 17.2-33.0%). Of the total study patients (n = 299), 48.5% were reported dead after allo-hematopoietic SCT, with disease progression as the first cause of death in PTCL patients. Although most studies included were retrospective and their sample size was small, existing data suggested that the group of PTCL patients receiving allo-SCT was to a great degree homogeneous regarding OS, mortality without relapse, death rate and the incidence of GVHD. The most common cause of death was disease progression. The present data did not show a difference in OS between allo- and auto-SCT in PTCL patients, but large prospective studies are needed to provide a more comprehensive understanding of the role of allo-SCT in the treatment of PTCL patients.

Pilot study using tacrolimus rather than cyclosporine plus antithymocyte globulin as an immunosuppressive therapy regimen option for severe aplastic anemia in adults.

Severe aplastic anemia (SAA), which is considered to be an immune-mediated destruction of bone marrow stem cells with pancytopenia and hypoplasia, can be successfully treated with immunosuppressive therapy or hematopoietic stem cell transplantation (HSCT). Between January 2009 and December 2012, thirteen patients diagnosed with SAA were treated with tacrolimus plus rabbit antithymocyte globulin (ATG)-based immunosuppressive therapy (IST). The outcomes were then compared with our previous data for twenty-four patients administered with cyclosporine (CsA) plus rabbit ATG-based IST. All 37 cases accepted methylpredenisolone and recombinant human granulocyte colony-stimulating factor (rhG-CSF) from the first day that rabbit ATG was initiated. A total of 7 (54%) of the 13 patients in the tacrolimus group and 10 (42%) of the 24 cases in the ATG+CsA group achieved the criteria for complete response (CR); the partial response (PR) rate was 31% in the tacrolimus group and 33% in the ATG+CsA group. The median follow-up duration of the tacrolimus group and ATG+CsA group patients was 28 months and 27 months, respectively. Two patients in the tacrolimus group who were red blood cell- and platelet transfusion-dependent died, one of sepsis and the other of cerebral hemorrhage, whereas one patient died from serious infection on the 5th day after ATG was initiated in the ATG+CsA group. No clonal transformation to paroxysmal nocturnal hemoglobinuria (PNH) was observed in either group. Our data provide a possibility of using tacrolimus as part of an IST regimen for SAA in adults who have no opportunity of HSCT from human leukocyte antigen (HLA)-matched sibling donors.

Comparative long-term prognosis of early surgery and surgery after surveillance for patients with ground-glass nodule adenocarcinomas.

To compare the pathological results and long-term survival results of early surgery and surgery after at least one year follow-up for ground-glass component predominant lung adenocarcinoma patients. From January 1, 2013 to August 31, 2017, a total of 279 patients with ground-glass nodules (GGNs) undergoing surgical resection and pathologically proved to be pulmonary adenocarcinoma were included in this study. All patients were divided into early surgery group (ES Group) (210 cases) and surgery after follow-up group (FS Group) (69 cases). Patients in FS group experienced at least one year surveillance. Clinical and imaging features were analyzed by using univariate analysis. After analysis, there was no statistical difference in pathological results and long-term prognosis between the two groups. In the follow-up group, grown GGNs have proved to have more aggressive pathological results. The one-year follow-up may be a feasible management method for patients with ground-glass component predominant GGN.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide.

BACKGROUND: Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. OBJECTIVE: We aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). STUDY DESIGN: SAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. RESULTS: All 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein-Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. CONCLUSION: rhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

INTRODUCTION: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. METHODS: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. RESULTS: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. CONCLUSION: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

Upper gastrointestinal tract immune-related adverse events: Two cases of obstructive complications occurred in immune consolidation therapy after sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation for refractory/relapsed diffuse large B cell lymphoma.

Key Clinical Message: Immune checkpoint inhibitors are a very popular method of treating malignant tumors. But its side effects cannot be ignored. This study revealed obstructive complications during immune consolidation therapy following sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation in two patients with diffuse large b cell lymphoma (DLBCL). Both our patients had the same symptoms of vomiting and inability to eat due to pyloric obstruction, it should be highlighted that this is a relatively rare and irreversible complication of upper gastrointestinal caused by immune consolidation therapy. Abstract: Immune checkpoint inhibitors (ICIs) have become the standard therapy for many malignant tumors.However, ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation and associated complications have been observed in patients. Here, we report two cases of patients with pyloric obstruction and duodenal ulcers induced by the use of sintilimab, which provides some guidance for the widely used anti-programmed death-1 therapy. During the entire treatment progression for such patients, the correct differential diagnosis of adverse effects and the use of immunosuppressive agents such as glucocorticoids are essential to facilitate early prevention and intervention of irAEs.

Increased plasma indoleamine 2,3-dioxygenase activity and interferon-γ levels correlate with the severity of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism that plays an important role in the induction of immune tolerance. To evaluate the expression levels of IDO and interferon (IFN)-γ in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify the correlation between IDO activity, IFN-γ, and acute graft-versus-host disease (aGVHD), we measured IDO mRNA expression in peripheral blood mononuclear cells in 89 allo-HSCT patients by reverse transcription-polymerase chain reaction. The IDO activity in plasma was also performed by reverse-phase high-performance liquid chromatography; plasma IFN-γ was detected by a standard enzyme-linked immunosorbent assay. IDO mRNA was detected in 55 of 74 patients (74.32%) with aGVHD. Of patients without aGVHD, only 2 of 26 expressed IDO mRNA (7.69%); none of 8 healthy volunteers was positive for IDO expression. Plasma IDO activity was much higher in aGVHD patients than in those without aGVHD (4.74 ± 3.35 vs 1.79 ± 1.02, respectively; P < .0001) or in healthy control subjects (4.74 ± 3.35 vs 1.77 ± .22; P < .0001). Patients with severe (grade III/IV) aGVHD had much higher IDO activity than those with mild (grade I/II) aGVHD (6.57 ± 3.34 vs 2.46 ± 1.41; P < .0001). Meanwhile, there was a significant increase in plasma IFN-γ level in aGVHD patients (P = .0043). IDO activity decreased after alleviation of aGVHD, whereas fluctuation of plasma IDO was also observed upon the recurrence of aGVHD. Plasma IDO activity was correlated with the level of plasma IFN-γ (r = .8288; P < .0001). Using receiver-operating characteristic curves analysis, the sensitivity and specificity for evaluation of aGVHD were determined. The area under the curve of IDO activity was higher than that of IFN-γ (.852 vs .694) with a sensitivity and specificity for IDO of 81% and 78%, respectively, whereas the sensitivity and specificity for IFN-γ were 41% and 93%, respectively. IDO mRNA was expressed in blood mononuclear cells of patients with aGVHD. Plasma IDO activity was elevated in aGVHD patients and was correlated with the severity of aGVHD. In combination with plasma IFN-γ, IDO activity may represent a potential biomarker for the diagnosis and evaluation of aGVHD after allo-HSCT. Intervention of the IDO pathway may also represent an alternative way to overcome steroid-resistant aGVHD.

Association of human leukocyte antigen class I polymorphism with spontaneous clearance of hepatitis B surface antigen in Qidong Han population.

AIM: To investigate whether HLA class I polymorphisms could influence the clearance of hepatitis B surface antigen (HBsAg) in Qidong Han population. METHODS: We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV persistent infection and 140 persons with spontaneous clearance of HBsAg by polymerase chain reaction with sequencing based typing (PCR/SBT). All the individuals were unrelated males enrolled from Qidong Han population and were followed up for 10 years. RESULTS: The frequency of HLA-A∗33:03:01G was increased in persistent HBV infection group (P value is 0.028), while frequency of HLA-B∗13:01:01G was increased in HBsAg clearance group (P value is 0.0004). CONCLUSION: These findings suggested that the host HLA class I polymorphism is an important factor in determining the outcomes of HBV infection.

Combination of human leukocyte antigen and killer cell immunoglobulin-like receptor genetic background influences the onset age of hepatocellular carcinoma in male patients with hepatitis B virus infection.

To investigate whether killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P = 0.04 for KM analysis; HR = 1.70, P = 0.004 for multivariate Cox model). We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells) in the progress of HBV-related HCC development.

The Dislocation- and Cracking-Mediated Deformation of Single Asperity GaAs during Plowing Using Molecular Dynamics Simulation.

This work simulates the plowing process of a single asperity GaAs by diamond indenter using molecular dynamics simulations. The deformation mechanism of asperity GaAs is revealed by examining the topography evolution and stress state during the plowing. This work also investigates the origin of the influence of asperity size, indenter radius and plow depth on the deformation of the asperity GaAs. We observed the initiation and propagation of cracks up to the onset of fracture and the plastic activity near the indenter, obtaining more information usually not available from planar GaAs in normal velocity plowing compared to just plastic activity. The simulations demonstrated the direct evidence of cracking in GaAs induced by plowing at an atomic level and probed the origin and extension of cracking in asperity GaAs. This finding suggests that cracking appears to be a new deformation pattern of GaAs in plowing, together with dislocation-dominated plasticity modes dominating the plowing deformation process. This work offers new insights into understanding the deformation mechanism of an asperity GaAs. It aims to find scientific clues for understanding plastic removal performed in the presence of cracking.

Case Report: Metagenomic Next-Generation Sequencing Can Contribute to the Diagnosis and Treatment of Disseminated Visceral Kaposi Sarcoma Following Allogeneic Haematopoietic Stem Cell Transplantation.

Disseminated visceral Kaposi sarcoma (KS) following allogeneic haematopoietic stem cell transplantation (HSCT) is a rare but life-threatening posttransplant complication. A suitable management strategy for disseminated KS involvement in transplant patients is unclear. Here, we reported a patient who developed disseminated visceral KS following HSCT, which was the first detailed report documenting the relationship among KS development, delayed immune reconstitution, and HHV-8 DNA levels by metagenomic next-generation sequencing (mNGS). The HHV-8 viral load peaked at 2071 sequence reads with an absolute lymphocyte count of 0.17×109/L on day +242. On day +536, the HHV-8 viral load became undetectable, with an absolute lymphocyte count of 1.06×109/L and the KS disappearance. HHV-8 load in blood detected by mNGS may be used as an early prediction marker for KS, a guide for early withdrawal of immunosuppression, and a tool to monitor KS treatment response in the setting of HSCT, especially in patients with CMV-seropositive or graft failure postengraftment. Through whole-exome sequencing, we explored the molecular mechanism underlying the patient's longer latency of haematopoietic or immune reconstitution and recurrent infections. Germline mutations in the FANCI and RAD51 genes might impair the patient's DNA repair ability, leading to a degree of immunodeficiency and tumour susceptibility. We strongly recommended evaluating the clinical history of the donor and investigating whether there were possible germline mutations suspected for immunodeficiency or familial neoplasms. Disseminated visceral KS patients could likely benefit from chemotherapy, especially if the disease appears to be aggressive.

CAR T-Cell Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma with Progressive Muscular Dystrophy: A Case Report.

Muscular dystrophies are a heterogeneous group of genetically inherited degenerative disorders defined by dystrophic features on pathological assessment of muscle biopsy specimens. Muscular dystrophies and lymphoma are not common concomitant diseases. Chimeric antigen receptor (CAR) T-cell immunotherapy for lymphoma patients with inherited degenerative diseases, such as muscular dystrophies, has not been previously reported. We report a relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patient with progressive muscular dystrophy (PMD) characterized by progressive muscle weakness that affected the limb, axial and facial muscles. He was identified to be a germline DYSF p.R204* homozygous mutation carrier. The patient received a murine monoclonal anti-CD19 and anti-CD22 CAR T-cell "cocktail" and suffered from a mild case of grade 1 cytokine release syndrome (CRS). One month after the CAR T-cell infusion, he achieved complete remission of his lymphoma without minimal residual disease (MRD), as assessed by radiography. One year after the infusion, the Deauville score was stable at 1. Currently, patient has been in remission for over three years after receiving anti-CD19 and anti-CD22 CAR T-cell therapy. This case provides evidence for the use of CAR T-cell therapy in lymphoma patients with inherited degenerative disorders. Achieving remission of the lymphoma and subsequent administration of γ-globulin as well as zoledronic acid reduced the muscular dystrophy symptoms.

Sequential CAR T-Cell Therapy After Autologous Stem Cell Transplantation for the Treatment of Relapsed/Refractory Intravascular Large B-Cell Lymphoma With Central Nervous System Involvement: A Case Report.

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive, large B-cell non-Hodgkin's lymphoma. The prognosis of IVLBCL in patients with central nervous system recurrence after first-line chemotherapy treatment is extremely poor. Among immunotherapies, chimeric antigen receptor (CAR) T-cell immunotherapy has been recently found to be a highly effective treatment for B-cell lymphoma, especially for relapsed or refractory diffuse large B-cell lymphoma. However, no guidelines are available that provide a clear consensus regarding the management of patients with relapsed/refractory IVLBCL. Here, we report, for the first time, the use of autologous hematopoietic stem cell transplantation (ASCT) and CAR T-cell therapy in a patient with relapsed/refractory IVLBCL. Case Presentation: A 42-year-old woman was diagnosed with IVLBCL based on liver biopsy and developed central nervous system (CNS) progression. The patient received ASCT combined with murine monoclonal anti-CD19 and anti-CD22 CAR T-cell therapy. She achieved complete remission for 22 months so far with negative minimal residual disease and continues to be followed up. Conclusion: ASCT combined with CAR T-cell therapy was the best choice for treatment of relapsed/refractory IVLBCL, as it allowed the achievement of a lasting complete remission.

Mosaic Trisomy 21 and Trisomy 14 as Acquired Cytogenetic Abnormalities without GATA1 Mutation in A Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia.

One case of acute megakaryoblastic leukemia (AMKL) with trisomy 21, trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported. The patient experienced transient myelodysplasia before the onset of AMKL. The bone marrow blasts manifested typical morphology of megakaryoblast both by the May-Giemsa staining and under the electronic microscopy. Leukemic cells were positive for CD13, CD33, CD117, CD56, CD38, CD41 and CD61 in flow cytometry analysis. Cytogenetic study showed karyotype of 48, XX, +14, +21 in 40% metaphases. Known mutations of GATA1 gene in Down syndrome or acquired trisomy 21 were not detected in this case.

Long event-free survival after anti-BCMA CAR-T cell treatment for relapsed and refractory multiple myeloma patients: Two case reports.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used in the treatment of relapsed and refractory multiple myeloma (RRMM). The response rate and the depth of responses induced by anti-BCMA CAR-T cells are impressive. However, despite this, remissions are not sustained, and the majority of patients eventually relapse. PATIENT CONCERNS: Two patients with multiple myeloma (MM) were selected to enroll in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113) because they did not have the good effect after traditional treatment. One is a 48-year-old male patient who received a diagnosis of IgG lambda MM in June 2015, he has received 4 cycles of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and obtained a complete response (CR). Approximately 11 months later, the disease progressed. Subsequent treatment included regimens incorporating liposomal doxorubicin, bortezomib, and dexamethasone (3 cycles); the response was poor, and the disease kept progressing. Another 65-year-old female patient received a diagnosis of IgG lambda MM in September 2016, she has received induction therapy with 1 cycle of bortezomib and dexamethasone (VD) and 4 cycles of lenalidomide and dexamethasone, the response was poor. DIAGNOSIS: Both patients were diagnosed with RRMM according to the International Myeloma Working Group criteria. INTERVENTIONS: Both patients received infusions of anti-BCMA CAR-T cells following an induction chemotherapy regimen of cyclophosphamide and fludarabine. OUTCOMES: Both of them achieved a stringent CR at the 30th day with minimal residual disease-negative bone marrow by flow cytometry and serum monoclonal protein was undetectable at 4 and 10 months after cell transfusion. The CR has persisted in the 2 patients for >36 months. CONCLUSIONS: Our findings demonstrate the anti-BCMA CAR-T cell treatment is a feasible therapeutic option for patients with RRMM. Fewer early lines of treatment may be beneficial to maintain the efficacy of CAR-T cells. TRIAL REGISTRATION: ChiCTR-OPC-16009113.

Allogeneic Hematopoietic Stem Cell Transplantation Mobilized With Pegylated Granulocyte Colony-Stimulating Factor Ameliorates Severe Acute Graft-Versus-Host Disease Through Enrichment of Monocytic Myeloid-Derived Suppressor Cells in the Graft: A Real World Experience.

We compared the effectiveness and safety of pegylated granulocyte colony-stimulating factor (peg-G-CSF) vs. non-peg-G-CSF for hematopoietic stem cell mobilization in allogeneic hematopoietic stem cell transplantation in a real-world setting. We included 136 consecutive healthy donors treated with non-peg-G-CSF (n = 53) or peg-G-CSF (n = 83), and 125 consecutive recipients (n = 42 and 83, respectively) in this study. All harvesting was completed successfully. No significant difference in leukapheresis number and adverse events frequency was observed, nor were there severe adverse events leading to discontinuation of mobilization. The leukapheresis products mobilized by peg-G-CSF had higher total nucleated cells (p < 0.001), monocytic myeloid-derived suppressor cells (p < 0.001), granulocytic myeloid-derived suppressor cells (p = 0.004) and B cells (p = 0.019). CD34+ cells and other lymphocyte subsets (T cells, regulatory T cells, natural killer [NK] cells, etc.) were similar in both apheresis products. Patients who received grafts mobilized by peg-G-CSF exhibited a lower incidence of grade III-IV acute graft-versus-host disease (p = 0.001). The 1-year cumulative incidence of chronic graft-versus-host disease and relapse, 1-year probability of graft-versus-host disease-free relapse-free survival, and overall survival did not differ significantly between subgroups. Our results suggest that collecting allogeneic stem cells after the administration of peg-G-CSF is feasible and safe. Peg-G-CSF mobilized grafts may reduce severe acute graft-versus-host disease compared with non-peg-G-CSF mobilized grafts after allogeneic stem cell transplantation. The beneficial effects of a peg-G-CSF graft might be mediated by increased numbers of monocytic myeloid-derived suppressor cells.