[Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Outcomes of haploidentical peripheral blood stem cell transplantation following myeloablative conditioning using two types of rabbit ATG: a propensity score-matched analysis.

During hematopoietic stem cell transplantation (HSCT), ATG depletes T cells in-vivo to improve engraftment and prevent graft-versus-host disease (GVHD). Here, we compared the clinical efficacy of two different types of ATGs: thymoglobulin and anti-human T-lymphocyte immunoglobulin (Grafalon). A total of 469 patients who received haploidentical transplantation were enrolled in this retrospective study. We applied a propensity score (PS)-matched analysis and 209 patients were assigned to each group. Clinical outcomes were compared between two groups and primary outcome was overall survival (OS). There was no significant difference in OS between two groups. Within the first 180 days after HSCT, Grafalon was associated with lower incidences of Epstein-Barr virus (EBV) viremia (31.6 vs. 54.5%, P < 0.0001) and cytomegalovirus viremia (CMV) viremia (54.5 vs. 67.9%, P = 0.005) compared to thymoglobulin. Patients receiving Grafalon had a higher rate of moderate/severe chronic GVHD (26.3 vs. 18.2%, P = 0.046). However, the incidences of engraftment failure, grade II-IV acute GVHD, relapse, non-relapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) did not differ greatly between groups. In the subgroup analysis, Grafalon improved the OS of lymphoid malignancies with young ages (< 40 years old) (HR, 0.55; P = 0.04) or with a high/very high disease risk index (HR, 0.36; P = 0.04). In the myeloid cohort, Grafalon reduced NRM in the patients who received non-female for male transplantation grafts (HR, 0.17; P = 0.02). Our results suggest the two types of ATG may differentially influence transplant outcomes and it may optimize ATG selection according to the condition of patients.

A case of peripheral T-cell lymphoma in which therapy-related myelodysplastic syndrome developed and a second autologous transplantation was performed.

We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide versus HLA-Matched Unrelated Donor Transplantation for Myelodysplastic Syndrome.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole curative therapy for myelodysplastic syndrome (MDS). In the absence of an HLA-matched sibling donor, an HLA-matched unrelated donor (MUD) is considered the leading candidate. However, in recent decades, the alternative donor pool has been extended to HLA-haploidentical donors, especially with the development of graft-versus-host disease (GVHD) prophylaxis using post-transplantation cyclophosphamide (PTCy). Comparative data for haploidentical and MUD allo-HCT in patients with MDS are scarce. We retrospectively analyzed 697 adult patients with MDS who underwent HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with PTCy (n = 136), MUD bone marrow transplantation (MUD-BMT) (n = 465), or MUD peripheral blood stem cell transplantation (MUD-PBSCT) (n = 96) as their first allo-HCT between 2014 and 2020 using Japanese registry data. Multivariable analyses demonstrated faster neutrophil engraftment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.65 to 2.90; P < .001) and platelet engraftment (HR, 2.31; 95% CI, 1.72 to 3.10; P < 0001) in the MUD-PBSCT cohort compared with the haplo-PBSCT cohort. MUD-BMT was associated with a higher incidence of grade II-IV acute GVHD than haplo-PBSCT (HR, 1.52; 95% CI, 1.00 to 2.29; P = .048). Among patients without in vivo T cell depletion using antithymocyte globulin (ATG) (haplo-PBSCT, n = 136; MUD-BMT, n = 446; MUD-PBSCT, n = 65), MUD-PBSCT recipients experienced faster hematopoietic recovery, MUD-BMT recipients (HR, 1.54; 95% CI, 1.02 to 2.32; P = .042) or MUD-PBSCT recipients (HR, 1.83; 95% CI, 1.06 to 3.18; P = .03) had a higher incidence of grade II-IV acute GVHD, and MUD-PBSCT recipients developed chronic GVHD more frequently than haplo-PBSCT recipients (HR, 1.74; 95% CI, 1.04 to 2.89; P = .034). There were no significant differences in overall survival, disease-free survival, GVHD-free relapse-free survival, relapse, or nonrelapse mortality in the haplo-PBSCT cohort versus the MUD-BMT or MUD-PBSCT cohorts. In conclusion, despite differences in the incidences of hematopoietic engraftment and GVHD depending on graft type and ATG use in MUD transplant recipients, major transplantation outcomes were comparable between recipients of haplo-PBSCT using PTCy and recipients of MUD-BMT or MUD-PBSCT.

Peripheral blood stem cell transplantation vs. bone marrow transplantation for aplastic anemia: a systematic review and meta-analysis.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst. Results: We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT. Conclusion: Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, CRD42023412467.

[A retrospective analysis of 124 patients with multiple myeloma who received up-front autologous hematopoietic cell transplantation following triplet induction therapy].

The IFM/DFCI group reported that VRD induction followed by up-front autologous peripheral blood stem cell transplantation (ASCT) and maintenance therapy led to median PFS of 50 months, which established up-front ASCT as the standard of care even in the era of novel agents. We conducted a retrospective analysis on outcomes of patients who received triplet induction therapy followed by up-front ASCT at our institution. A total of 124 patients received ASCT between November 2016 and December 2021 at Japanese Red Cross Medical Center. Patient characteristics, treatment response before and after ASCT, and PFS and OS were retrospectively analyzed. VRD-based induction therapy was used for 94%. Among 118 evaluable patients, 116 (98%) received either consolidation and/or maintenance therapy. Best responses were ≥CR 77% and ≥VGPR 94%, respectively. Sixty-eight out of 104 patients achieved MRD-negativity by multiparameter FCM (<10-5). Five-year estimated PFS and OS were 54.7% and 80.2%, respectively. Age ≥65, high-risk cytogenetic abnormalities, and

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.

Assessing the cognition, attitudes and intentions of volunteers regarding unrelated peripheral blood stem cell donation: The UPBSC-DQ instrument in Chinese.

Objectives: This study aimed to develop and validate the Unrelated Peripheral Blood Stem Cell Donation Questionnaire (UPBSC-DQ) (an instrument in Chinese) to assess the degree of cognition, attitude and intention of enrolled volunteers towards UPBSC donation. Methods: The development process of the UPBSC-DQ was performed in a stepwise approach that included extensive literature retrieval, expert revision, and pretesting with 442 students. We conducted an online cross-sectional survey using the final version of the UPBSC-DQ among 336 participants. The reliability of the questionnaire was assessed by Cronbach's α and corrected item-total correlation (CITC), and the validity was evaluated by a correlation coefficient matrix, confirmatory factor analysis (CFA), and t-test. Results: The UPBSC-DQ consists of four domains: basic information, cognitive, attitude, and intention. The Cronbach's α values were 0.88 and 0.86 for the attitude and intention scales, respectively, indicating strong internal consistency and good reliability. Correlation analysis and CFA showed good structure and content validity. Interitem correlations indicated that each item had only a weak correlation with the other scales. Conclusions: The UPBSC-DQ is a reliable and valid assessment questionnaire for individuals' attitudes and intentions towards UPBSC donation. The questionnaire showed good to high reliability, content and construct validity.

The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study.

BACKGROUND: Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge. METHODS: Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed. RESULTS: MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004). CONCLUSIONS: Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.

Case report: Allogeneic stem cell transplantation for type B insulin resistance.

Type B insulin resistance (TBIR) is a rare, often fulminant form of insulin resistance caused by autoantibodies against the insulin receptor. If left untreated, its mortality is high. Various immunosuppressive regimens have shown efficacy, but treatment effects are variable and time-delayed, and drug-induced complications may arise. We report a patient with TBIR arising as a complication of Wiskott-Aldrich syndrome. Stable remission of TBIR was achieved through allogeneic peripheral blood stem cell transplantation (PBSCT) over a follow-up period of more than 1.5 years. We thus demonstrate that PBSCT can be considered a treatment option in TBIR where conventional immunosuppressive therapy is ineffective or contraindicated.

Economic analysis of allogeneic hematopoietic stem cell transplantation in the Bone Marrow Transplant Center of Tunisia.

Introduction: New procedures and diagnostic tests in hematopoietic stem cell transplantation (HSCT) are associated with a significant increase in costs. The last cost estimate of allogeneic HSCT done in Tunisia was in 1996 and concerned only direct medical costs. Therefore, an updated cost analysis is needed. Objective: Analysis of direct costs during the first-year post-allogeneic HSCT in two groups of patients: Bone Marrow Transplant (Allo-BMT) and Peripheral Blood Stem Cell Transplant (Allo-PBSCT) and identification of factors leading to interindividual variations in costs in order to compare these costs with the budget allocated by the payer (CNAM). Methods: Pharmacoeconomic retrospective study, concerning patients who underwent allogeneic HSCT in 2013. Clinical and unit cost data were obtained from medical and administration records. Results:This study showed that the average direct cost of allogeneic HSCT in the population during the first year reached 56 638€. The average cost of Allo-BMT was 63 612€, and Allo-PBSCT was 45 966€ (p > 0.05). The initial hospitalization counted for 88% of total direct cost with an average cost of 41 441€ in Allo-BMT and 24 672€ in Allo-PBSCT (p < 0.05). Direct medical costs represented more than 70% of total direct costs, drugs, and laboratory tests occupied the largest share. Antifungals, antitumors, and antiviral drugs were the most expensive pharmaceutical classes with a mean cost, respectively, of 4 526€; 3 737€ and 3 268€. Some clinical criteria were significantly related to total direct costs like length of aplasia (p < 0.01) and GVHD (p < 0.05). However, the type of blood disease, its risk, length of mucositis, and the treatment protocol have no effect on the costs for all allogeneic patients. Conclusion: Our results showed that the costs of Allo HSCT have exceeded by far the budget allocated by the CNAM to the center, since the 90s to this day. That's why the total reimbursement mechanism should be revised.

Aortitis after administration of pegfilgrastim to a healthy donor for peripheral blood stem cell collection.

A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of pegfilgrastim (Day 4) and 4.32 × 106 /kg of CD34-positive cells per recipient body weight were obtained. Fever of 38 ℃ or higher and left submandibular pain appeared on Day 6. Ultrasonography and contrast-enhanced computed tomography (CT) showed wall thickening of the carotid artery and the abdominal aorta. We carefully excluded the possibilities of cardiovascular and autoimmune diseases by thorough examination, and ultimately diagnosed pegfilgrastim-induced aortitis. The patient's fever resolved rapidly after treatment with prednisolone (PSL) 1 mg/kg. We began to taper PSL after eight days. Sixty-one days after starting PSL, we confirmed that abdominal aortic wall thickening had improved by contrast-enhanced CT. We continued to taper off PSL and stopped 141 days later with no relapse thereafter. This is the first case report of pegfilgrastim-induced aortitis in an allo-PBSCT donor. Careful monitoring is warranted when administering pegfilgrastim to donors even without past medical history.

Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature.

A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

High levels of NK Cells in graft are associated with reduced febrile neutropenia after haploidentical peripheral blood stem cell transplantation.

OBJECTIVE: To investigate the impact of natural killer (NK) cells in the graft on the outcome following haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). METHODS: We retrospectively collected data from patients who had undergone haplo-PBSCT at our centre from January 2019 to November 2021. The percentage of NK cells in stem cell grafts was detected by flow cytometry. Based on the median (range) count of NK cells (1.8 [0.4-6.0] × 108/kg), patients were separated into high and low NK cell count groups. RESULTS: Data from 96 patients were analysed. Patients were evenly distributed (48 in each group) into high and low NK cell count groups. There was no significant difference in neutrophil and platelet recovery between the two groups. However, the rates of febrile neutropenia, bacterial infection, and invasive fungal disease (IFD) were significantly reduced in the high compared with the low NK cell count group. There was no significant difference in rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections between groups. There was no significant difference between groups in grades II and above acute graft versus host disease (GVHD), progression-free survival (PFS), or overall survival (OS). CONCLUSION: A high number of NK cells in the graft may reduce febrile neutropenia, IFD and bacterial infection following haplo-PBSCT but it has no significant effect on aGVHD, PFS, or OS.

Pleuroparenchymal fibroelastosis secondary to autologous peripheral blood stem cell transplantation: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonitis. Although most cases of PPFE are idiopathic, some cases of PPFE occur secondary to stem cell transplantation. We report a 41-year-old woman developed pneumonia after autologous peripheral blood system cell transplantation (PBSCT). Eleven years after PBSCT, she presented with dyspnea. A computed tomographic scan showed pleuroparenchymal thickening and predominantly in the upper lobes. She was diagnosed with PPFE secondary to PBSCT. She was started nintedanib and administered oxygen therapy. Most cases of PPFE secondary to stem cell transplantation have been reported. However, we experienced the case of PPFE post-autologous PBSCT.

Efficacy and safety of allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients aged > 65 years with unfavorable cytogenetics.

Unrelated donor bone marrow transplantation (UR-BMT), unrelated donor cord blood stem cell transplantation (UR-CBT), and haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) are the main alternative stem cell sources for allogeneic hematopoietic cell transplantation (HCT) in Japan. The present study aimed to identify factors associated with the outcomes of UR-BMT, UR-CBT, and Haplo-PBSCT in older patients with acute myeloid leukemia (AML) and intermediate- or poor-risk cytogenetics to improve the clinical efficacy and safety of allogeneic HCT. We retrospectively analyzed data for 448 AML patients aged > 65 years who received UR-BMT (n = 102), UR-CBT (n = 250), or Haplo-PBSCT (n = 96) between 2014 and 2020. Overall survival (OS) in the UR-BMT group was superior (P = 0.033) to that in the other groups. However, all patients without complete remission (non-CR) who had Karnofsky performance status (KPS) < 80 at HCT and poor-risk cytogenetics died within 1 year after HCT. Multivariate Cox regression analysis identified KPS <80 at HCT and poor-risk cytogenetics as independent predictors of worse OS in non-CR patients. KPS < 80 may be an alternative indicator for non-CR AML patients with poor-risk cytogenetics during the selection of HCT, alternative treatments, or best supportive therapy, and the optimal KPS is important for the success of HCT.

Autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia is safe but poses challenges for long-term maintenance of molecular remission: Results of the Auto-Ph17 study.

Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto-PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34+ cells was harvested in all five patients. No patient died within 100 days after auto-PBSCT, and no unexpected serious adverse events were observed. Although 1-year event-free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389-1088 days) after auto-PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto-PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto-PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long-term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long-term molecular remission.

Post-transplantation cyclophosphamide combined with tacrolimus and low-dose post-engraftment anti-thymoglobulin as GVHD prophylaxis for patients undergoing peripheral blood stem cell transplantation from haploidentical family donor: A single center analysis.

Introduction: Post-transplantation cyclophosphamide (PT-Cy) use is a recent graft-versus-host disease (GVHD) prophylaxis strategy for patients undergoing allogeneic stem cell transplantation (allo-HSCT). PT-Cy combined with two immunosuppressants is now widely used after haplo-identical (haplo) and HLA-matched peripheral blood stem cell (PBSC) transplantations with promising GVHD and relapsefree survival (GRFS) probabilities. Although appealing, these results may benefit from improvement notably outside matched sibling donor transplantation, and should be investigated in various ethnic populations. Methods: Therefore, we report our experience of GVHD prophylaxis regimen combining PT-Cy and tacrolimus with addition of post-engraftment low-dose anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation from haplo-identical donors (Haplo). Sixtyseven patients were included in the analysis. All patients received myeloablative or intensified sequential conditioning regimen. Results: The median follow-up was 521 (range, 10~991) days. The cumulative incidences of 100-day grade II-IV acute GVHD was 14.9±4.4%, and no case of grade III-IV acute GVHD was documented. The cumulative incidences of 2-yearchronic GVHD and moderate-to-severe chronic GVHD were 25.4±5.4% and 11.9±4%, respectively. The non-relapse mortality at day+100 and 2year were 7.5±3.2% and 9.0±3.5%, respectively. The cumulative incidence of relapse at 2year was 16±6.4%. The 2-year probability of DFS and OS were 73.8% (95%CI, 61.5~88.4%) and 72.5% (95% CI, 57.1~92.1%), respectively. The 2-year GRFS was estimated as 63.6% (95%CI, 50.6~80%). Discussion: Our results suggested that a combination of PT-Cy, tacrolimus, and low-dose post-engraftment ATG was a promising GVHD prophylaxis with low incidence of acute GVHD in the haplo-transplantation setting.

Unique Reduced-Intensity Conditioning Haploidentical Peripheral Blood Stem Cell Transplantation Protocol for Patients with Hematologic Malignancy.

Reduced-intensity conditioning (RIC) haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) requires more hematopoietic progenitor and stem cells (HPSCs) to promote engraftment and immune reconstitution and needs a stronger graft-versus-leukemia effect. Peripheral blood stem cells (PBSCs) offer advantages over bone marrow; however, the use of higher-dose non-T cell-depleted (non-TCD) in vitro PBSCs may increase the occurrence of severe graft-versus-host disease (GVHD). This prospective, single-arm clinical study was performed to investigate using high-dose non-TCD in vitro PBSCs as the graft source, using fludarabine/Ara-C/busulfan (FAB) as the conditioning regimen, using rabbit antithymocyte globulin to remove T cells in vivo, and enhancing GVHD prophylaxis with an IL-2 receptor antagonist in RIC-haplo-HSCT in patients with hematologic malignancies age 50 to 70 years or <50 years with comorbidities (Hematopoietic Cell Transplantation Comorbidity Index score ≥2) classified as intermediate to high risk. The primary endpoint was day 100 acute GVHD (aGVHD). A total of 47 patients were enrolled; the median age was 52 years (range, 30 to 68 years), the median duration of follow-up was 34 months (range, 2 to 99 months), and the medium-infused doses of mononuclear cells, CD34+ cells, and CD3+ cells were 15.93 × 108/kg, 8.68 × 106/kg, and 5.57 × 108/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day 100 was 30.3% (95% confidence interval [CI], 15.9% to 44.8%), and that of grade III-IV aGVHD was 10.2% (95% CI, .6% to 19.8%). The 2-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI, 19.0% to 50.8%). The 2-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI, 11.80% to 40.40%) and 8.7% (95% CI, 3.26% to 20.65%), respectively. The 2-year cumulative incidence of relapse was 17.3% (95% CI, 5.1% to 29.5%), the 2-year overall survival rate was 71.2% (95% CI, 57.9% to 84.5%), and the 2-year disease-free survival rate was 66.2% (95% CI, 52.1% to 80.3%). The incidence of aGVHD was not high, and the overall efficacy was good. This study demonstrates that this unique RIC-haplo-PBSC transplantation protocol was effective in treating hematologic malignancies. Nonetheless, larger prospective multicenter clinical trials and experimental studies should be performed to further confirm our findings.

Eight-color multiparameter flow cytometry (EuroFlow-NGF) is as sensitive as next-generation sequencing in detecting minimal/measurable residual disease in autografts of patients with multiple myeloma.

The prognostic value of minimal/measurable residual disease (MRD) detection in autografts of patients with multiple myeloma (MM) in an autologous stem-cell transplantation setting has been reported. Next-generation flow (NGF) cytometry has lower sensitivity (2 × 10-6) to detect MRD than next-generation sequencing (NGS) (<10-6). We compared the clinical value of high-sensitivity NGF (cutoff: <10-6) and NGS (cutoff: 10-6) for the detection of MRD in the cryopreserved autografts of 49 patients with newly diagnosed MM. The sensitivity test using frozen/thawed autografts revealed a strong correlation among MRD levels of 5 × 10-7 and 1 × 10-4 (r = 0.9997, p < 0.0001) when an adequate number of cells were analyzed. Autograft MRD levels determined using NGF and NGS were highly correlated (r = 0.811, p < 0.0001). MRD-negative patients identified with NGF (cutoff: <10-6) showed significantly longer progression-free survival (PFS) than MRD-positive patients (p = 0.026). The PFS of MRD-negative patients determined by NGS (cutoff: 10-6) was similar to that determined by NGF. These results show that the high-sensitivity NGF method can assess MRD in frozen/thawed autografts, and its prognostic value is comparable to that of NGS.