Blood Hematopoietic Stem Cell Transplantation Research Articles

Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation

To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation. A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed. Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05). Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

Chains of Iron in Umbilical Cord Blood Hematopoietic Stem Cell Transplantation: Comment on "Iron Overload Is Associated with Delayed Engraftment and Increased Nonrelapse Mortality in Recipients of Umbilical Cord Blood Hematopoietic Cell Transplantation" by Al Malki et al, 2020.

Abstract Comment on “Iron Overload is Associated with Delayed Engraftment and Increased Non-Relapse Mortality in Recipients of Umbilical Cord Blood Hematopoietic Cell Transplantation” by Al Malki et al. 2020

Advances in Sickle Cell Disease Treatments.

Sickle Cell Disease (SCD) is an inherited disorder of red blood cells that is caused by a single mutation in the β -globin gene. The disease, which afflicts millions of patients worldwide mainly in low income countries, is characterized by high morbidity, mortality and low life expectancy. The new pharmacological and non-pharmacological strategies for SCD is urgent in order to promote treatments able to reduce patient's suffering and improve their quality of life. Since the FDA approval of HU in 1998, there have been few advances in discovering new drugs; however, in the last three years voxelotor, crizanlizumab, and glutamine have been approved as new therapeutic alternatives. In addition, new promising compounds have been described to treat the main SCD symptoms. Herein, focusing on drug discovery, we discuss new strategies to treat SCD that have been carried out in the last ten years to discover new, safe, and effective treatments. Moreover, non-pharmacological approaches, including red blood cell exchange, gene therapy and hematopoietic stem cell transplantation will be presented.

Research Advances on Ex Vivo Expansion Strategy of Hematopoietic Stem Cells--Review

Abstract Hematopoietic stem cells (HSCs), as a kind of adult stem cell, is first used in clinical practice. It has been widely used in hematopoietic stem cell transplantation and has broad application prospects in the field of gene therapy. However, the shortage of HSC is still the main bottleneck restricting the clinical application of HSC transplantation, especially cord blood HSC transplantation. With the continuous improvement of the concept of HSC and the in-depth study of the molecular mechanism regulating HSC self-renewal and differentiation, it have been explored that a variety of strategies for ex vivo expansion of HSC, such as adding small molecule compounds in vitro culture system, simulating bone marrow microenvironment, regulating HSC metabolism and biomaterial-based amplification methods. In this review, recent advances in research of ex vivo expansion strategy of HSC are summarized and discussed.

Outcome of donor lymphocyte infusion for fall in chimerism after hematopoietic stem cell transplant

Achievement of complete donor chimerism after an allogeneic hematopoietic stem cell transplant is necessary for elimination of underlying malignant disease. A decline in donor chimerism may herald an impending relapse and therefore, early recognition and intervention plays an important role in such cases. A 32 year old male patient diagnosed as a case of Philadelphia positive mixed phenotypic acute leukaemia underwent peripheral blood hematopoietic stem cell transplant (HSCT) with his sibling as donor. During follow-up, a fall in donor chimerism was observed from 91.86% on day +37 to 88.83% on day +57 and 85.34% on day +77. Donor Lymphocyte Infusion (DLI) was harvested via apheresis. A dose of 1 × 106 per kg was infused and the rest was cryopreserved in aliquots of escalating doses. On day +102, he presented with biopsy proven acute mucocutaneous GVHD grade 2 which was managed conservatively and donor chimerism of 57.99%. On day +126, a repeat donor chimerism was performed which showed 100% chimerism. He continues to do well at day +161. Timely use of DLI can improve donor chimerism in patients with Philadelphia positive acute leukaemia who tend to relapse after HSCT.

Clinical and Pathological Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

To explore the clinical manifestation, pathological features and treatment regimen of blastic plasmacytoid dendritic cell neoplasm (BPDCN). The clinical and pathologic features, diagnosis, treatment and prognosis of 5 BPDCN patients were analyzed retrospectively. 5 patients had skin lesions, and bone marrow involvement. The immunohistochemical staining showed that the CD56 expression was observed in 5 patients, CD4 and CD123 in 4 patients, and CD43 expressed in 3 patients. After initial treatment, 3 patients achieved complete remission and 1 patient did not. One patient showed disease progression after partial remission for 1 month. Two young patients underwent sibling allo-PBHSCT, and then achieved long-term survival. BPDCN often presents skin lesions as the first symptom, moreover, soft tissues, lymph nodes and bone marrow were involved, which suggested the disease progresses. There is currently no uniform treatment protocol for this disease. Active allogeneic peripheral blood hematopoietic stem cell transplantation in the CR1 phase for appropriate patients may increase their chances for long-term survival.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.

Protective Effects of Cytomegalovirus DNA Copies ≧1000/mL for AML Patients in Complete Remission After Single Cord Blood Transplantation.

IntroductionCurrent consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited.Patients and MethodsWct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies <1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls.ResultsThe results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07–0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8+ T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20×109/L vs 0.10×109/L, p=0.021, respectively).ConclusionDNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8+ T cells.

Improvement of Survival in JMML By Induction Regimen of Decitabine + Cytarabine + Fludarabine before Hematopoietic Stem Cell Transplantation: Study of 33 Cases in Single Center

OBJECTIVE: Pre-transplant chemotherapy can control progression of primary disease, alleviate disease and improve disease-free survival after transplantation in juvenile granulocyte leukemia (JMML).Methylation abnormalities play an important role in the development of JMML. This study was to explore the effectiveness of induction regimen including decitabine ,cytarabine and fludarabine before transplantation and to explore the affection to transplantation in JMML. METHODS: A retrospective analysis of the remission and survival of 33 children with JMML before and after stem cell transplantation in the Department of Pediatrics of Nanfang Hospital from 2014.2 to 2019.7. There were fourteen girls and 19 boys, median diagnosis age 23 months(2m-10 years old). Median white blood cell count,median hemoglobin level,median platelet count( WBC) was 29.3G/L (6.29-158.66G/L); 83g /L(41-113g/L,); 27.17G / L(4-431G / L) respectively. Median Hemoglobin F level was 34.16%( 1.56-78%). Median spleen level under the costal margin was 5cm(0-13.3cm); Median liver under the costal margin was 3.9 cm(0 -8.9 cm) .There were 26 cases with the pulmonary involvement (26/33, 78.8%). The original blast cells in bone marrow were 0-8.8%, with a median of 4.5%.Mutant genes including: 2 cases of KAS, 9 cases of NF1, 2 cases of NRAS, 16 cases of PTPN11, and 4 cases without common JMML gene .The first course of treatment after diagnosis is 20 mg/m2 × 5 days of decitabine. The second course of treatment is DA: decitabine 20 mg/m2 × 5 days + cytarabine 100 mg/m2 × 5 days or A-3V regimen: Ara-C 100 mg/m2/d CIV×7 days+Etoposide 100 mg/m2/d ×5 days+Vincristine 1.5 mg/m2/d ×1 day. The third course of treatment is decitabine 20 mg/m2 × 5 days,then FLAG regimen: Fludarabine 30mg / m2 × 5 days, Ara-C 1 g / m2 × 5 days, G-CSF 5μg / Kg × 6 days. Single drug of decitabine 20 mg/m2 × 5 days was adminstered 1-3 times per monthly during the period of waiting for transplantation. Comprehensive assessment was performed before transplantation. Survival outcomes were analyzed by Kaplan-Meier curves. RESULTS: At least 3 courses of chemotherapy were completed in 33 cases, including 1-5 courses of decitabine.The bone marrow was evaluated in 31 patients before transplantation: 12 patients got complete remission(CR) and 19 patients got partial remission(PR) .Peripheral blood evaluation: 23 cases achieved WBC CR; 17 cases achieved platelet CR, 6 cases achieved platelet PR, 7 cases had no improvement. Eighteen cases of spleen were evaluated, of which only 3 cases were CR, 13 cases were PR, and 2 cases did not improve. Overall assessment, only 1 case achieved CR before transplantation, 1 case did not improve, and 31 cases achieved PR .Allogeneic hematopoietic stem cell transplantation was performed in 33 cases, including 3 cases of nonrelated peripheral blood hematopoietic stem cell transplantation(PB HSCT), 30 cases of complementary transplantation (haploid identical PB HSCT plus non-related cord blood transplantation). The median follow-up time after transplantation was 22m(3-63m).There was no death in the period of chemotherapy before transplantation. Four patients relapsed after transplantation, and One patient died of transplantation related death. Three years EFS was 80.6%. Conclusion: Pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine is safe, effective and feasible. The response rate of treatment is 97.0%, although the complete remission rate before transplantation is low, most of them are partial remission, but the disease-free survival after non-related HSCT or complementary transplantation could reached to 80.6%. These results indicated that pre-transplant chemotherapy based on regimen of decitabine + cytarabine + fludarabine was benefit to improved the survival of children with JMML after HSCT. Figure 1 Disclosures No relevant conflicts of interest to declare.

Tocilizumab for Prophylaxis of Cytokine Release Syndrome after Outpatient-Based Haploidentical T-Cell Replete Peripheral Blood Stem Cell Transplantation

Introduction Cytokine release syndrome (CRS) is a common and potentially severe toxicity associated with haploidentical peripheral blood hematopoietic stem cell transplantation (Haplo-HSCT). CRS is characterized by immune activation and a high level of circulating inflammatory cytokines, particularly interleukin-6 (IL-6). While tocilizumab, an IL-6 receptor-targeted monoclonal antibody has been effectively used to treat CRS in the context of immunotherapy, it has not been evaluated during the acute Haplo-HSCT period. We hypothesized that prophylactic tocilizumab can prevent CRS after Haplo-HSCT. We report the results of a pilot trial to evaluate its use. Methods Patients ≥18 years undergoing Haplo-HSCT of peripheral blood in a single center with any underlying diagnosis were included. The conditioning was myeloablative and was administered as follows: cyclophosphamide 350 mg / m2 and fludarabine 25 mg / m2 (days -5-3) or rabbit antithymocyte globulin (2.5 mg / kg days -4, -3), plus melphalan 200 mg / m2 PO (days -2-1). Prophylaxis of graft versus host disease (GVHD) consisted of cyclophosphamide (50 mg / kg / day, days +3 and +4), cyclosporine and mycophenolate mofetil on day +5. The cells were infused on day 0. Tocilizumab was administered on day -1 in a single dose of 4 mg / kg IV. CRS was rated according to Lee et al. The primary outcome included the incidence and severity of CRS, the adverse effects associated with tocilizumab, hospitalization and graft rates and the incidence of GVHD. Results Ten patients have enrolled, with an average age of 26 years (range 19-32). The underlying diagnoses were acute lymphoblastic leukemia (n = 7), acute myeloid leukemia (n = 1) and non-Hodgkin lymphoma (n = 2). There were no infusion reactions associated with tocilizumab. Six patients (60%) developed CRS, all grades 1-2, with a median day of onset on day +2 (range 1-3) and a median fever duration of 2 days (range 2-3), often accompanied by nausea, diarrhea, dehydration and transaminitis. All patients were hospitalized; hospitalization was not related to CRS in three patients. 4 patients are alive without relapse (40%), 2 patients alive with relapse (20%), 3 patients died due to transplant-related mortality (30%), one patient dies from relapse (10%). No graft failure occurred and mixed chimerism was observed in a patient. Acute GVHD with steroid response has been diagnosed in 2 cases (20%, grade I / II). The median follow-up is 8.3 months (range 0-20). Conclusion What we observe about the prophylactic use of tocilizumab for Haplo-HSCT of peripheral blood is that its administration is feasible, Grades 1-2 CRS was observed in 60% of patients, grades 3-4 were not observed, however the use of tocilizumab did not prevent hospitalizations. More feasibility data is required before starting a definitive randomized trial to evaluate the use of tocilizumab for Haplo-HSCT peripheral blood. Disclosures Gomez-Almaguer: Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. OffLabel Disclosure: Tocilizumab for Prophylaxis of Cytokine Release Syndrome

One and Half Million Hematopoietic Stem Cell Transplants (HSCT). Dissemination, Trends and Potential to Improve Activity By Telemedicine from the Worldwide Network for Blood and Marrow Transplantation (WBMT)

HSCT is the only curative option for many malignant and non-malignant diseases. The WBMT was founded as an umbrella organization of societies involved in cellular therapies with the mission of promoting excellence in HSCT. As a non-governmental organization in official relation with the World Health Organization (WHO), the WBMT assisted in the founding of regional societies (Latin America Blood and Marrow Transplantation Group and African Blood and Marrow Transplantation Group), performs global activity surveys, conducts workshops and provides expert support for programs in evolving countries. In this retrospective evaluation we analyzed worldwide activity trends in HSCT up to the year 2016 and evaluated possibilities of improving availability of HSCT by the use of telemedicine. Methods: HSCT activity was collected annually from member societies, national registries and individual centers including donor type (allogeneic/autologous), stem cell source (bone marrow/peripheral blood stem cells/cord blood) and indications for transplant. Transplant rates (TR) were calculated as HSCT/10 million inhabitants without adjustment for patients transplanted in a country other than that of primary residence. Country team density (TD) was defined as teams/10 million inhabitants. Workshops were organized in a number of locations where there was little or no HSCT activity or where improvement in one or more aspect of local or regional HSCT activity was requested, including Vietnam, Brazil, China, South Africa and Morocco. Other countries were paired with established centers using WBMT affiliated partners. In two countries, a pilot program was established involving a 6 month physician training in a JACIE/FACT accredited center followed by daily telemedicine-guided supervision of clinical activities. Results: From 1957-2016 a total of 1,298,897 HSCT (57.1% autologous) procedures were collected. By the end of 2016, HSCT activity was reported from 87 of the 195 WHO member states. A total of 89,070 HSCT from 1662 centers was reported in 2016. Assuming a frequency of 84,000/year, 1.5 million HSCT will be reached in 2019, only 7 years after the 1 million report in 2012 (Figure 1). The global activity/year increased continuously from 10,000/year in 1991 to 82,718 first HSCT/year in 2016 with a global increase of &gt;7% (7.0% in autologous and 7.8% in allogeneic HSCT). As in previous years, slightly more autologous (53.5%) than allogeneic and more related (53,6%) than unrelated HSCT were reported. The further increase in related HSCT was caused mainly by an increase of non-identical family donors (39.5% of related HSCT). Increase in activities according to regions is given in Figure 2. TR and TD varied according to region and are highest in Nord America with 511.2 TR, followed by Europe with 390.9 TR, Latin America with 63.9 TR, APBMT with 46.2 TR and Africa/EMRO with 32.8 TR. In contrast, TD was highest in Europe (7.5 TD) followed by Nord America (6.0 TD), APBMT (1.9 TD), Latin America (1.9 TD) and Africa/EMRO (0.4 TD). Commonest indications were lymphoproliferative diseases for autologous and leukemia for allogeneic HSCT and continue to rise (Figure 3 autologous and Figure 4 allogeneic HSCT). Graft source were predominantly peripheral blood in autologous (99.7%) and 65% in unrelated HSCT, while umbilical cord blood as a stem cell source (13.8% of all unrelated) declined. More than 150 HSCT were performed in one country and one center without activities using daily telemedicine-guided supervision. In conclusion, the global distribution and activities are increasing continuously by more than 7,0% per year with numbers currently running at app. 90,000/year. Of note is the increase of haploidentical HSCT activity, while the use of umbilical cord blood HSCT continues to decrease. TR data show significant gaps between regions. Supervisory telemedicine is a powerful tool to overcome lack of experience and establish JACIE/FACT compatible new programs with collateral benefits for conventional hematology, blood banking, microbiology and virology. Abbreviations: EUR, Europe; AMR/PHA, America; SEAR/WPR, South-East Asia/Western Pacific; AFR/EMRO, African/Eastern Mediterranean. Disclosures Niederwieser: Daichii: Speakers Bureau; Cellectis: Consultancy. Atsuta:Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Mochida Pharmaceutical Co. Ltd: Honoraria; Janssen Paharmaceutical K.K.: Honoraria. Worel:Sanofi Genzyme, Malinckrodt Therakos: Research Funding; Jazz, Sanofi, Celgene, Novartis, Malinckrodt Therakos: Honoraria; Sanofi Genzyme, Malinckrodt Therakos: Speakers Bureau. Galeano:Szabo SA: Other: (Equity interest). Novitzky:Astellas, Roche: Consultancy. Szer:Prevail Therapeutics: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Alexion: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Weisdorf:Incyte: Research Funding; Pharmacyclics: Consultancy; Fate Therapeutics: Consultancy. Pasquini:Amgen: Consultancy; BMS: Research Funding; Medigene: Consultancy; Pfizer: Other: Advisory Board; Novartis: Research Funding; Kit Pharma: Research Funding.

Retrospective Evaluation of the Use of Romiplostim after Hematopoietic Stem Cell Transplantation0

Background Prolonged thrombocytopenia following hematopoietic stem cell transplant (HSCT) is a common complication associated with risks of major bleeding and high platelet transfusion requirements. Although not approved in the setting of post-HSCT thrombocytopenia, few case series have investigated the use of thrombopoietin (TPO)-receptor agonist romiplostim for patients receiving HSCT. Herein, we reviewed its use in the setting of HSCT at our Institution. Methods From January 2006 to December 2017, 4642 patients received a first HSCT. Of these patients, 2152 (46%) received an autologous HSCT (auto-HSCT) while 2490 (54%) received an allogeneic HSCT (allo-HSCT). Among the patients in the allo-HSCT group, 752 (30%) received a matched related HSCT, 1125 (45%) a matched unrelated HSCT, 278 (11%) a mismatch unrelated HSCT and 335 (13%) a cord blood HSCT. A reduced intensity conditioning regimen was used in 629 (25%) patients receiving an allogeneic HSCT. An adequate clinical response was considered as a reduction of transfusion requirement and a platelet count PLT ≥ 50*103 /µL. This research was approved by the Institutional Review Board (IRB). Results Seven patients (adults n=5, children n=2) received romiplostim for thrombocytopenia. Patients' characteristics are reported in Table 1. All but one (who had CLL-related ITP) received the drug while in remission for the underlying hematologic disease. Romiplostim was used in 6 patients after an allo-HSCT and in 1 after an auto-HCT. Among the allo-HSCT recipients, all 6 reached neutrophil engraftment at a median time of 19 days (range 14-28 days). Romiplostim was administered for ITP (n=2) and poor graft function (PGF, n=4), at a median time of 7.5 months (range 2 - 34 months), with a median of 16 administrations (range 3-18) per patient. All patients received romiplostim weekly, with a median initial and maximum dose of 1 µg/kg (range 1-3 µg/kg) and 9.5 µg/kg (range 3-10 µg/kg), respectively. For the 2 ITP cases, romiplostim was given as third line of therapy, after a lack of response to both high dose steroids and intravenous immunoglobulin. One patient responded to the treatment, achieving a platelet count ≥ 50*103/µL after 2 months, while the other patient did not show any improvement and the drug was discontinued after 3 months. All the 4 PGF cases were thought to be secondary to medications, with one patient also having acute graft versus host disease (GvHD) as possible cause. Romiplostim was given as first line of treatment in all the cases; median platelet counts at the time of starting the treatment was 21*103/µL (range 13-42*103/µL). One patient did not show any response after 4 months of treatment and was subsequently switched to another TPO receptor agonist. Three patients showed a clinical benefit: one patient achieved a stable platelet count ≥50*103/µL after one month, another patient had a partial response achieving transfusion-independence after 3.5 months, but with PLT counts remaining below 50*103/µL; the third patient had a transient increase in platelet counts with decreased transfusion requirement, but the response was lost after two weeks. Overall romiplostim was well tolerated, with no major side effects related to its administration. In two cases mild increase in reticulin stain (grading 0-1) was observed. The auto-HSCT patient receiving romiplostim had Hodgkin's Lymphoma and was diagnosed with recurrent ITP 7.5 years after HSCT, while in complete remission for the underlying disease; he received romiplostim as part of the ITP treatment, and responded to a combination of romiplostim and mycophenolate mofetil without reporting adverse events. Conclusion In our analysis, the use of romiplostim was limited to very few cases of HSCT. The retrospective nature of this study along with a very small and heterogeneous cohort does not allow us to draw any efficacy conclusions. However, our data suggest that romiplostim could be considered a safe option to treat prolonged thrombocytopenia after HSCT. Prospective, randomized clinical trials using TPO-receptor agonists for thrombocytopenia in HSCT are needed to determine efficacy and potential side effects. Disclosures Lawrence: Amgen Inc.: Employment, Equity Ownership. Gernsheimer:Dova pharmaceuticals: Consultancy; Novartis: Honoraria; Amgen: Consultancy, Honoraria; Rigel: Consultancy; Shionogi: Consultancy; Cellphire: Consultancy; Fuji film: Consultancy; Bioverativ: Consultancy. Milano:Amgen: Research Funding; ExCellThera: Research Funding. OffLabel Disclosure: We investigated the use of Romiplostim for thrombocytopenia after hematopoietic cell transplant.

Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial.

Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited. The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma following autologous peripheral blood HSCT were assessed. Eighty patients (age: 18-68years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25μg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated. Median time to ANC engraftment (≥0.5 × 103/μl: 10.0 vs. 11.0days; P = 0.98) and PC engraftment (≥20.0 × 103/μl: both 14.0days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/μl: 13.0 vs. 20.0days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/μl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/μl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72). Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT. Graphical abstract Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.

Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease

AbstractCardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.

APPLICATION OF POSITRON EMISSION TOMOGRAPHY / COMPUTER TOMOGRAPHY FOR EVALUATING THE RESPONSE TO CHEMOTHERAPY IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA / LYMPHOBLASTIC LYMPHOMA

Introduction.No recommendations are currently available on the use of positron emission tomography / computer tomography (PET/CT) for evaluating the response to chemotherapy in patients with acute lymphoblastic leukosis / lymphoblastic lymphoma (ALL/LBL).Aim. The aim of this research was to study the ability of tumour cells to accumulate radiopharmaceuticals during PET/CT in patients with ALL/LBL, as well as to evaluate the prognostic value of PET/CT results performed after completion of consolidation therapy with/without autologous hematopoietic blood stem cell transplantation (auto-HSCT) in patients with Ph-negative ALL/LLL who underwent therapy according to the protocols of a Russian research group ALL-2009/ALL-2016.Materials and methods.PET/CT was performed in 3 patients with various variants of a newly diagnosed ALL before the onset of therapy and after the completion of induction therapy. In 10 patients with Ph-negative ALL/LLL, a PET study was performed after consolidation had been completed according to the ALL-2009/ALL-2016 protocol.Results. The results of PET/CT in 3 patients with different variants of newly detected ALL/LBL were analysed. All patients showed a metabolic activity of 18F-FDG in all morphologically and immunohistochemically (immunophenotypically) confirmed lesions. An analysis of the PET/CT results in 10 patients with Ph-negative ALL/LBL after completion of consolidation therapy with/without auto-HSCT showed that all patients had achieved a PET-negative disease remission. With a median follow-up of 20.5 months (from 15 to 44 months), only one out of 10 patients demonstrated isolated neurorecurrence 10 months after achieving remission. The remaining 9 patients, under a median relapse-free survival rate of 19 months (from 14 to 43 months), demonstrated complete clinical and hematological remission.Conclusion. Specific medullary and extramedullary lesions in ALL/LBL are capable of accumulating 18F-FDG in PET, which allows the method under study to be used for evaluating the completeness of remission in extramedullary lesions. The prognostic feasibility of PET/CT under the involvement of the central nervous system remains to be studied.

Reduction of Opioid Use by Acupuncture in Patients Undergoing Hematopoietic Stem Cell Transplantation: Secondary Analysis of a Randomized, Sham-Controlled Trial.

To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation. Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P = 0.86). Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients.

Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis

The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.

ABO Blood Type Incompatibility Is Not a Risk Factor of Outcomes for Acute Myeloid Leukemia (AML) Patients After Unmanipulated Haplo-identical Peripheral Blood Hematopoietic Stem Cell Transplantation.

BackgroundHaplo-identical hematopoietic stem cell transplantation (HSCT) has provided potential donors for patients lacking available HLA-matched donors. ABO blood type compatibility has been reported to be associated with HSCT outcomes. However, few studies have investigated the role of ABO compatibility in haplo-identical HSCT of AML patients.Material/MethodsWe retrospectively analyzed 42 adult acute myeloid leukemia (AML) patients who received unmanipulated haplo-identical peripheral blood HSCT at the Chinese PLA General Hospital between Jan 2013 and Dec 2017. We analyzed the role of ABO compatibility in engraftment, transfusion requirements, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia, acute graft-versus-host disease (GVHD), overall survival (OS), transplantation-related mortality (TRM), relapse, chronic GVHD, and post-transplant lymphoproliferative disorder (PTLD).ResultsThere were no significant differences between the ABO-matched group and the ABO-mismatched group in terms of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. Univariate analysis revealed ABO incompatibility is not an independent risk factor of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. We found a significantly higher cumulative incidence of aGVHD in the matched group compared with the mismatched group (80.95% vs. 42.86%, p=0.020). In multivariate analysis, ABO mismatch was associated with decreased risk of acute GVHD within 100 days after transplant (hazard ratio 0.492, 95% confidence interval 0.2123–1.14). However, the difference was not statistically significant (p=0.099).ConclusionsThis study demonstrated ABO incompatibility is not an independent risk factor of outcomes for AML patients who received unmanipulated haplo-identical peripheral blood HSCT. ABO compatibility might have limited value in haplo-identical donor selection.

Clinical Efficacy of Modified BU/CY as Conditioning Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Young Acute Myeloid Leukemia Patients with Low or Intermediate Risk

To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission (CR1). Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation（allo-HSCT）and underwent auto-PBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after auto-PBHSCT, the maintenance therapy with interleukin-2 (IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality (TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemia-free survival (LFS) rate at 2 years and 3 years, overall survival (OS) were evaluated at 3 years and 4 years. Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred, but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count (ANC)<0.5×109/L and for platelet count <20.0×109/L were 1.5 (0-3) days and 3 (2-5) days after transplantation, respectively. The patients achieved ANC>0.5×109/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×109/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100% (10 cases) and 80% (8 cases), respectively. The 3-year and 4-year OS were 80% (8 cases) and 70% (7 cases), respectively. Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without highrisk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.

Comparison of umbilical cord blood transplantation and hematopoietic stem cell transplantation from HLA-matched sibling donors in the treatment of myelodysplastic syndrome-EB or acute myeloid leukemia with myelodysplasia-related changes

目的比较非血缘脐血干细胞移植（UCBT）与同胞HLA全相合供者造血干细胞移植（MSD-HSCT）治疗骨髓增生异常综合征伴原始细胞增多（MDS-EB）和急性髓系白血病伴骨髓增生异常相关改变（AML-MRC）的临床疗效。方法回顾性分析2011年2月至2017年12月接受UCBT/MSD-HSCT的MDS-EB/AML-MRC患者64例，其中MDS-EB 38例，AML-MRC 26例。结果①与MSD-HSCT组比较，UCBT组AML-MRC患者比例较高[52.8%（19/36）对25.0%（7/28），P=0.025]，中位年龄较低[13（1.5~52）岁对32（10~57）岁，P=0.001]。②UCBT组与MSD-HSCT组+42 d粒细胞植入率均为100%，中位植入时间分别为17.5（11~31）d、11.5（10~20）d；UCBT组+100 d血小板植入率为91.4%，中位植入时间为40（15~96）d，MSD-HSCT组+100 d血小板植入率为100.0%，中位植入时间为15（11~43）d。③UCBT组和MSD-HSCT组比较，+100 dⅡ~Ⅳ度、Ⅲ/Ⅳ度急性GVHD累积发生率、180 d移植相关死亡率、3年累积复发率、3年总生存率和3年无病生存率差异均无统计学意义（P>0.05）。④UCBT组3年慢性GVHD、重度慢性GVHD的累积发生率均低于MSD-HSCT组[28.3%（95% CI 13.4%~45.3%）对67.9%（95%CI 46.1%~82.4%），P=0.002；10.3%（95%CI 2.5%~24.8%）对50.0%（95%CI 30.0%~67.1%），P<0.001]；UCBT组3年无严重急慢性GVHD及无复发生存（GRFS）率明显高于MSD-HSCT组[55.0%（95%CI 36.0%~70.6%）对28.6%（95%CI 13.5%~45.6%），P=0.038]。结论UCBT治疗MDS-EB/AML-MRC患者可获得比MSD-HSCT更好的移植后生存质量。