Search

The role of autologous hematopoietic stem cell transplantation (auto-HSCT) following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, its clinical efficacy as frontline therapy remains to be elucidated. This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients. We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone (year 2008-2014) from four hospitals. The median follow-up time was 29.4 months. Between the two treatment arms among the intermediate/high-risk DLBCL patients, the 3-year overall survival (OS) and progression-free survival (PFS) rates of patients given frontline auto-HSCT were 87.6% and 81.9%, respectively, and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9% and 59.59%, respectively. Compared with the chemotherapy-alone group, the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell (GCB) type. In addition, in the frontline auto-HSCT group, patients who achieved complete response (CR) at auto-HSCT had a longer survival time than those who did not achieve CR. Our results suggested that frontline auto-HSCT could improve the prognosis of intermediate/high-risk DLBCL patients.

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.

Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss–related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss–related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs

Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients.Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3° at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy.The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor.The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and no standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) for adult T-LBL and evaluated prognostic factors affecting survival. A total of 181 newly-diagnosed adult T-LBL patients were enrolled: 89 patients were treated with chemotherapy alone, 46 were allocated to the single auto-HSCT group, 46 were treated with tandem auto-HSCT. Median follow-up time was 37 months; the 3-year progression/relapse rate of the tandem auto- HSCT group was significantly lower than that of the single auto-HSCT and chemotherapy groups (26.5% vs. 53.1% and 54.8%). The 3-year progression- free survival (PFS) and overall survival (OS) rates of the tandem auto- HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplant impacted OS and PFS. Multivariate analysis identified that disease status after the first transplant was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8+CD28+/CD8+CD28– T-cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto- HSCT can be considered an optimal strategy for adult T-LBL patients. (Study registered at: ChiCTR-ONN-16008480).

PURPOSE Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT. PATIENTS AND METHODS We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m2 of rhG-CSF on days 0-5 and 5 mg/m2 of Dec on days 1-5) or no intervention (non–G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival. RESULTS The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non–G-Dec group ( P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non–G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed. CONCLUSION Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.

The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies. In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs. Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7 days. The overall IFD breakthrough rate (probable cases) for the ≥4 days prophylactic treatment (n = 445) group was 1.6% (95% Cl: 0.6%–3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%. The overall effective IFD remission rate of patients treated for ≥7 days with posaconazole was 56.0% and the effective remission rate of proven/probable/possible IFD cases was 59.3%. The effective remission rate of posaconazole as salvage therapy was 50% (95% CI: 32.4%–67.6%) including 75% (CI: 19.4%–99.4%) for Aspergillus infections. The present retrospective study confirmed posaconazole as IFD prophylaxis and medication for hematological malignancy patients undergoing various treatments in China.

Purpose: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an “off-the-shelf” allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027. Patients and Methods: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. Result: Robust expansion of CAR-T cells along with rapid eradication of CD7+ T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed. Conclusions: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted “off-the-shelf” allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.

HLA-haploidentical hematopoietic stem cell transplantation (HSCT) may be an option for severe aplastic anemia (SAA) patients. However, to date, no large-sample studies have been performed to determine which types of SAA patients are suitable for HLA-haploidentical HSCT. We retrospectively studied 189 consecutive patients with SAA who underwent HLA-identical or HLA-haploidentical HSCT at seven transplant centers in China. Propensity score matching (PSM) was applied in this study to reduce the influence of potential confounders. The 5-year overall survival (OS) rate was 72.0% in the HLA-haploidentical group and 76.5% in the HLA-identical group. The median time to achieve engraftment and the incidence of acute GVHD/chronic GVHD were not significantly different between the two groups. In the subgroup analysis, the outcome of patients older than 40 years in the HLA-haploidentical group was significantly poorer than that of patients younger than 40 years in the same group and that of patients older than 40 years in the HLA-identical group. Based on the above results, we suggest that HLA-haploidentical relative HSCT should be considered as a valid alternative option for patients younger than 40 years with SAA for whom no matched sibling donor is available.

A 27-year-old male with HIV-associated naïve and high-risk Burkitt’s lymphoma sequentially received short-term, high-dose non-myeloablative chemotherapy and autologous CD34-positive stem cell transfusion in the setting of combined antiretroviral therapy (cART). Prompt hematopoietic recovery was observed after 2 weeks and clinical remission from Burkitt’s lymphoma within approximately 30 months after transplantation. The HIV RNA load was inhibited persistently, and drug resistance was not observed. The CD4+ T cell count approached 323 cells/μL in a recent follow-up study. This case suggests that the use of intensive non-myeloablative chemotherapy with transplantation, combined with antiretroviral therapy, in HIV-related naive and high-risk Burkitt’s lymphoma was tolerated and safe.

HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective and immediate treatment for high-risk acute myeloid leukemia (HR-AML) patients lacking matched donors. Relapse remains the leading cause of death for HR-AML patients after haplo-HSCT. Accordingly, the prevention of relapse remains a challenge in the treatment of HR-AML. In a multicenter randomized controlled trial in southwestern China, 178 HR-AML patients received haplo-HSCT with conditioning regimens involving recombinant human granulocyte colony–stimulating factor (rhG-CSF) or non–rhG-CSF. The cumulative incidences of relapse and graft-versus-host disease (GVHD), 2-year leukemia-free survival (LFS), and overall survival (OS) were evaluated. HR-AML patients who underwent the priming conditioning regimen with rhG-CSF had a lower relapse rate than those who were treated with non-rhG-CSF (38.2%; 95% confidence interval [CI], 28.1% to 48.3% versus 60.7%, 95% CI, 50.5% to 70.8%; P < .01). The cumulative incidences of acute GVHD, chronic GVHD, transplantation-related toxicity, and infectious complications appeared to be equivalent. In total, 53 patients in the rhG-CSF–priming group and 31 patients in the non-rhG-CSF–priming group were still alive at the median follow-up time of 42 months (range, 24 to 80 months). The 2-year probabilities of LFS and OS in the rhG-CSF–priming and non-rhG-CSF–priming groups were 55.1% (95% CI, 44.7% to 65.4%) versus 32.6% (95% CI, 22.8% to 42.3%) (P < .01) and 59.6% (95% CI, 49.4% to 69.7%) versus 34.8% (95% CI, 24.9% to 44.7%) (P < .01), respectively. Multivariate analyses indicated that the 2-year probability of LFS of patients who achieved complete remission (CR) before transplantation was better than that of patients who did not achieve CR. The 2-year probability of LFS of patients with no M4/M5/M6 subtype was better than that of patients with the M4/M5/M6 subtype in the G-CSF–priming group (67.4%; 95% CI, 53.8% to 80.9% versus 41.9%; 95% CI, 27.1% to 56.6%; P < .05). This study suggests that the rhG-CSF–priming conditioning regimen is an acceptable choice for HR-AML patients, especially for the patients with no M4/M5/M6 subtype who achieved CR before transplantation.

In a well-controlled multi-center randomized trial in southwestern China, 228 patients with refractory or relapsed AML were received a low-dose CAG regimen either with etoposide (E-CAG) or without etoposide (CAG). The complete remission (CR) rate, overall survival (OS) and toxicity were evaluated. Patients with E-CAG had a higher CR rate (71.1% vs. CAG 50.9%, P=0.0002). The tolerability appeared to be equivalent. Patients with CR who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) had a higher five-year OS over those without allo-HSCT (73.8% vs. 10.8%, P=0.000). The E-CAG regimen is expected to become a bridge between relapsed or refractory AML and allo-HSCT.

Background Since the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients. Methods We analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients’ posttransplantation following detection of BCR-ABL transcripts. Results All of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p