Myeloproliferative neoplasm with eosinophilia and coexisting BCR::ABL1 and PDGFRB rearrangement: favorable and rapid response to imatinib.

Here, we present a rare case of myeloproliferative neoplasms (MPN) with eosinophilia harboring both BCR::ABL1 and PDGFRB rearrangements, posing a classification dilemma. The patient exhibited clinical and laboratory features suggestive of chronic myeloid leukemia (CML) and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), highlighting the diagnostic challenges associated with overlapping phenotypes. Despite the complexity, imatinib treatment swiftly achieved deep molecular remission, underscoring the therapeutic efficacy of tyrosine kinase inhibitors in such scenarios. Furthermore, the rapid attainment of deep remission by this patient in response to imatinib closely resembles that observed in MLN-TK patients with PDGFRB rearrangements. Further research is warranted to elucidate the underlying mechanisms driving the coexistence of multiple oncogenic rearrangements in MPNs and to optimize therapeutic strategies for these complex cases.

Case Report: Combination Therapy With PD-1 Blockade for Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation Resulted in Fatal GVHD.

Background: Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of this monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and their ligands, making the combination of HMAs and immune checkpoint blockade therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation. Case Presentation: We reported a case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT and was previously exposed to HMAs-based therapy. The patient received tislelizumab for compassionate use. After the combination treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease (MRD) by flow cytometry (FCM), and negative Wilms' tumor protein 1 (WT1). However, the patient successively developed serious immune-related adverse events (irAEs) and graft vs. host disease (GVHD) and eventually died from complications of GVHD. Conclusion: To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML posttransplantation. This report highlights the safety concerns of using an anti-PD-1 antibody in combination with azacitidine after allo-HSCT, especially the risk of GVHD, and provides a basis for future studies.

Myeloablative Haploidentical Transplant as an Alternative to Matched Sibling Transplant for Peripheral T-Cell Lymphomas.

The number of HLA-haploidentical allogeneic hematopoietic stem-cell transplantation (Haplo-HSCT) is increasing. Comparative studies about Haplo-HSCT versus allo-HSCT with HLA-matched sibling donors (MSD-HSCT) have been tried in leukemias and B-cell lymphomas. Few studies were reported in Peripheral T-cell lymphomas (PTCLs). We performed a multicenter retrospective study about 52 patients with PTCLs undergoing Haplo-HSCT (n = 20) or MSD-HSCT (n = 32). All Haplo-HSCT recipients received antithymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis. The median follow-up for all survivors was 38 months. The 100-day cumulative incidence of grade II to IV acute GVHD was similar (19% in the MSD-HSCT group versus 28% in the Haplo-HSCT group, P = 0.52). The 2-year cumulative incidence of chronic GVHD (limited and extensive) after Haplo-HSCT (30%) was also similar with that in the MSD-HSCT group (50%, P = 0.15). The 3-year relapse rates (33% vs 27%, P = 0.84) and non-relapse mortality (21% vs 22%, P = 0.78) did not differ between these two groups. There were also no differences in 3-year overall survival (OS) (48% vs 50%, P = 0.78) and progression-free survival (47% vs 51%, P = 0.95) between these two groups. On multivariate analysis, prognostic index for T-cell lymphoma (PIT) score (higher than 1: hazard ratio [HR], 4.0; P = 0.003) and disease status (stable or progression disease before HSCT: HR, 2.8; P = 0.03) were independent variables associated with worse OS. We concluded that ATG-based haplo-HSCT platform could work as an alternative to MSD-HSCT for patients with PTCLs.

Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .@*Methods@#The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.@*Results@#The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively.@*Conclusion@#ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient With FUS-ERG+ AML.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chemotherapy is part of standard treatment protocol for patients with acute myeloid leukemia (AML). FUS-ERG+ AML is rare but has an extremely poor prognosis even with allo-HSCT in remission, possibly due to its a leukemia stem cell (LSC)-driven disease resulting in chemotherapy resistance and a novel therapy is urgently required. It has been reported that FUS-ERG-positive AML expresses CD123, a marker of LSC, in some cases. CD123-targeted CAR T cell (CART123) is promising immunotherapy, but how to improve the complete remission (CR) rate and rescue potential hematopoietic toxicity still need to explore. Case Presentation: We used donor-derived CART123 as part of conditioning regimen for haploidentical HSCT (haplo-HSCT) in a patient with FUS-ERG+ AML who relapsed after allogeneic transplantation within 3 months, resists to multi-agent chemotherapy and donor lymphocyte infusion (DLI) and remained non-remission, aiming to reduce these chemotherapy-resistant blasts and rescue potential hematopoietic toxicity. The blasts in BM were reduced within 2 weeks and coincided with CAR copies expansion after CART123 infusion. The patient achieved full donor chimerism, CR with incomplete blood count recovery, and myeloid implantation. Conclusion: Our results hints that CART123 reduces the chemotherapy-resistant AML blasts for FUS-ERG+ AML without affecting the full donor chimerism and myeloid implantation.

The usage of comprehensive geriatric assessment in elderly patients with acute myeloid leukemia: a multicenter, prospective study / 中华血液学杂志

Objective@#To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China.@*Methods@#The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected.@*Results@#Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050).@*Conclusions@#CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma / 中华血液学杂志

Objective@#To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .@*Methods@#From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.@*Results@#Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) .@*Conclusion@#Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Comparative study on the efficacy and safety between pegfilgrastim (PEG-rhG-CSF) and recombinant human granulocyte colony-stimulating factor in promoting hematopoietic recovery after allogeneic hematopoietic stem cell transplantation after hematological malignancy / 中华血液学杂志

Objective@#To observe the efficacy and safety between Pegfilgrastim (PEG-rhG-CSF) and Recombinant human granulocyte colony stimulating factor (rhG-CSF) in hematological malignancy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#157 patients after allo-HSCT were enrolled in this study from June 2015 to November 2016. Two agents of G-CSF were used to stimulate hematopoietic recovery after transplantation. There were 65 cases in PEG-rhG-CSF and 92 cases in rhG-CSF groups. Patients in PEG-rhG-CSF group were given a single subcutaneous dose of 6 mg on the first day and +8 d, while cases in rhG-CSF group were given in dose of 5 μg·kg-1·d-1 by subcutaneous injection from +1 d continuing to neutrophils more than 1.5×109/L, and then the indicators and survival rates in two groups after transplantation were compared.@*Results@#①There were no significant differences of the neutrophil implantation time[13.5 (8-12) d vs 13 (9-24) d, P=0.393] and platelet implantation time [14 (9-160) d vs 14 (9-92) d, P=0.094] between PEG-rhG-CSF and rhG-CSF groups respectively. There were no significant differences in terms of neutropenia period (P=0.435) , number of cases who got fever during neutropenia (P=0.622) , and the median time of fever in neutropenia period (P=0.460) , respectively between the two groups. There were no significant differences of erythrocyte and platelet transfusions (P=0.074, P=0.059) within 1 month after transplantation. ②There were no significant differences with regard to the incidences of acute GVHD[23.1% (15/65) vs 34.8% (32/92) , P=0.115], chronic GVHD[20.0% (13/65) vs 32.6% (32/92) , P=0.081], Ⅱ-Ⅳdegree of acute GVHD[30.0% (13/65) vs 30.4% (30/92) , P=0.287] and extensive chronic GVHD[9.2% (6/65) vs 20.7% (19/92) , P=0.135] between PEG-rhG-CSF and rhG-CSF groups. ③There were no significant differences in terms of disease free survival (DFS) (62.5% vs 61.4%, P=0.478) and overall survival (OS) (67.4% vs 67.3%, P=0.718) between PEG-rhG-CSF and rhG-CSF groups. ④There was no significant difference of the non-relapse mortality (NRM) between PEG-rhG-CSF and rhG-CSF groups[20.5% (95%CI 11.4%-37.0%) vs 32.6% (95%CI 22.2%-47.9%) , P=0.141]. The relapse rate was not statistically significant[14.9% (95%CI 7.4%-29.8%) vs 10.0% (95%CI 5.0%-20.0%) , P=0.299].@*Conclusion@#Compared with rhG-CSF, PEG-rhG-CSF could reduce the times of injection. There were no differences in terms of hematopoietic recovery, the incidence of GVHD, relapse rate, DFS and OS rates after allo-HSCT between two groups.

Therapeutic effect of CY-fTBI and BMM conditioning regimen in the process of allo-HSCT treating Ⅲ,Ⅳ non-Hodgkin lymphoma: 15 years analysis of single-center / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in the treatment of patients with Ⅲ,Ⅳ non-Hodgkin lymphoma（NHL）, and compared the efficacy between Cy- fractionated to talbody irradiation（fTBI）based conditioning regimen and Maryland, horse flange and mitoxantrone（BMM）.</p><p><b>METHODS</b>The clinical data of 47 patients with Ⅲ, Ⅳ NHL after allo- HSCT from November 1998 to May 2014 were collected and retrospectively analyzed. To observe the hematopoietic reconstruction recovery after transplantation, cumulative incidence of acute graft- versus- host- disease （aGVHD） and chronic graft- versus- host- disease （cGVHD）, transplantation related mortality （TRM）, recurrence rate （RR）, disease- free survival （DFS）, overall survival（OS）. Compare the efficacy of fTBI and BMM conditioning regimen at the same time.</p><p><b>RESULTS</b>Neutrophils achieving 0.5×10⁹/L and platelets achieving 50×10⁹/L on day 17 （range, 10- 72） post transplantation. Acute GVHD occurred in 53.19%, among them, grade Ⅰ-Ⅱ occurred in 42.55%, grade Ⅲ-Ⅳ occurred in 10.65%, and cGVHD occurred in 21.28%. 21 patients were alive with a median follow up of 9.7 months（0.2-149.1 months）. Overall survival（OS）was 73.5%, 49.3%, 40.1% respectively in the first, third and fifth year in Cy-fTBI group; in BMM group it was 67.8%, 32.9% and 31.4% respectively, and disease-free survival（DFS）was 65.3%, 45.6%, 30.2% respectively in the first, third and fifth year. In Cy-fTBI group, the recurrence rate（RR）and transplantation related mortality（TRM）in the first year were 18.9%, 23.0% respectively, the third year were 19.5%, 38.3% and the fifth year were 35.2%, 39.2%. In BMM group, RR and TRM in the first year were 27.4%, 24.5% respectively, the third year were 38.9%, 46.4% and the fifth year were 39.2%, 48.2%. However, there was no significant difference in the indicator of OS, DFS, RR, TRM in the two groups.</p><p><b>CONCLUSION</b>Allo-HSCT could make some Ⅲ,Ⅳ NHL patients achieve long-term disease- free survival, but the TRM was still high relatively. Moreover, compared with the program of BMM conditioning regimen, Cy-fTBI might reduce the TRM and RR, meanwhile, increase the DFS and OS. However, due to the small number cases of two groups, there was no statistical significant difference.</p>

Granulocyte colony-stimulating factor-primed bone marrow: an excellent stem-cell source for transplantation in acute myelocytic leukemia and chronic myelocytic leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Steady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.</p><p><b>METHODS</b>A total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1) received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS]) were analyzed.</p><p><b>RESULTS</b>When compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P < 0.05). Incidence of grade III-IV acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC. Although the incidence of cGVHD in the G-BM group was similar to SS-BM, both were lower than G-PBSC (P < 0.05). G-BM and G-PBSC exhibited similar survival, LFS, and TRM, but were significantly different from SS-BM (P < 0.05). There were no significant differences in leukemia relapse rates among the groups (P > 0.05).</p><p><b>CONCLUSIONS</b>G-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.</p>

Expression of GATA-2 Gene and Immunoglobulin Heavy Chain Germline Gene C( micro ) in Leukemia Cells and Its Significance / 中国实验血液学杂志

To investigate the significance of GATA-2 and immunoglobulin heavy chain germline gene C( micro ) (IgH germline gene C( micro )) expression and coexpression in various leukemia cells, GATA-2 and IgH germline gene C( micro ) mRNA in bone marrow and peripheral blood cells from 63 leukemia patients were detected by reverse transcription-polymerase chain reaction (RT-PCR). No GATA-2 or IgH germline gene C( micro ) mRNA were detected in normal bone marrow and peripheral blood. GATA-2 mRNA were be detected in 91.3% patients with acute myeloid leukemia (AML), 75% patients with acute lymphoblastic leukemia (ALL) as well as 83.3% patients with chronic myeloid leukemia (CML-CP); IgH germline gene C( micro ) mRNA were be identified in 47.8% AML, 41.6% ALL, as well as 5.6% CML-CP. All patients with CML-AP and CML-BC expressed GATA-2 mRNA and partly expressed IgH germline gene C( micro ) mRNA. 47.8% AML and 41.6% ALL patients coexpressed GATA-2 and IgH germline gene C( micro ) mRNA. GATA-2(+) IgH germline gene C( micro )(+) cells of AML and ALL were mainly HLA-DR positive. As aberration of the transcription factors, GATA-2 and germline IgH germline gene C( micro ) gene might been linked to leukemogenesis. Various expression of GATA-2 and germline IgH germline gene C( micro ) gene in leukemia might correlated with the heterogeneous differentiation level of leukemia cells. The fact that leukemia with GATA-2(+) IgH germline gene C( micro )(+) coexpression indicated multilineage impairment of hematopoietic cells.