Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study / 中国当代儿科杂志

OBJECTIVES@#To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB).@*METHODS@#A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed.@*RESULTS@#Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05).@*CONCLUSIONS@#Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

Effects of FAC combined with Bu conditioning for SAA patients undergoing allogeneic stem cell transplantation / 西安交通大学学报(医学版)

【Objective】 To observe the effects of FAC combined with Bu conditioning for severe aplastic anemia (SAA) patients undergoing allogeneic hematopoietic stem cell transplantation. 【Methods】 The data of 28 SAA patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital from January 2016 to September 2021 were collected and analyzed. The patients were divided into two groups: FAC conditioning group and FAC + Bu conditioning group. We observed the side effects of conditioning regimen, hematopoietic recovery, acute and chronic graft versus host disease (GVHD), viral infection, incidence of venous obstructive disease (VOD), progression free survival (PFS), and overall survival (OS). 【Results】 There was no significant difference between the two groups in age, gender, physical condition, history of disease, gender relationship between donors and recipients, transplantation type, infusion of bone marrow nucleated cells, MNC or CD34 positive cells (P>0.05). Compared with those in FAC group, the side effects of auditory hallucination and visual hallucination in FAC + Bu group increased, the incidence of mixed chimerism decreased, the time of platelet reconstruction shortened, the incidence of grade Ⅲ-Ⅳ aGVHD increased. However, 3-year PFS or OS did not significantly differ between the two groups. 【Conclusion】 FAC combined with Bu conditioning regimen promotes implantation and reduces mixed chimerism. However, it does not improve patients’ overall survival.

The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.@*METHODS@#The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.@*RESULTS@#Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.@*CONCLUSION@#The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Clinical observations of the therapeutic effect of CLAG or FLAG bridging BuCy conditioning regimen in the treatment of childhood acute leukemia / 中国输血杂志

【Objective】 To determine the therapeutic efficacy of cladribine combined with BuCy conditioning regimen for childhood acute leukemia, and compare it with fludarabine. 【Methods】 The clinical data of 70 children with acute leukemias who underwent all-HSCT from August 2018 to June 2020 were collected. The data of pretreatment-related toxicity, hematopoietic reconstitution, graft-versus-host disease, virus infection, relapsed and survival between CLAG and FLAG group were statistically analyzed. 【Results】 EBV infection in CLAG group was significantly more than that in FLAG group(P0.05). Multivariate analysis showed that there was no significant difference in the effect of conditioning regimen on relapsed and survival. Among other risk factors, types of diseases were significantly correlated with OS (P<0.05, HR: 0.088). Relapse was significantly correlated with bone marrow morphological remission before transplantation and the matching degree of donor and recipient HLA(P<0.05, HR: 34.678; P<0.05, HR: 0.024). 【Conclusion】 There was no significant difference in RRTs, hematopoietic reconstitution, GVHD occurrence, OS and relapsed between CLAG group and FLAG group. The overall efficacy of CLAG group was not inferior to FLAG group.

Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children / 中国当代儿科杂志

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.

Optimization and clinical application of the preconditioning regimen in the treatment of severe aplastic anemia with interfamilial haploidentical peripheral hematopoietic stem cell transplantation: A report of 26 cases / 解放军医学杂志

Objective To evaluate the safety and efficacy of an further optimized pretreatment protocol for the treatment of severe aplastic anemia (SAA) by haploidentical peripheral hematopoietic stem cell transplantation. Methods From July 2009 to July 2019, 26 SAA patients in the Affiliated Hospital of North China University of Technology were treated with haploidentical peripheral blood stem cell transplantation. The "Beijing protocol" of haploid transplantation for treating SAA is modified busulfan (BU)/cyclophosphamide (CY) + rabbit anti thymocyte globulin (ATG) regimen. We based on it and further refined it. Here's how it works: (1) According to the different volumes of hematopoietic tissue in bone marrow biopsy before transplantation, different methods for clearance of residual hematopoietic cells were established in SAA patients. If bone marrow hematopoietic tissue volume<10%, the bone marrow was pretreated with Beijing protocol of BU/CY+ATG. If 10% ≤ bone marrow hematopoietic tissue volume ≤25%, the dose of BU for 1 day was added on the basis of the original protocol: Increase the dose of BU to 9.6 mg/kg (intravenous drip in 3 days), which became a modified BU/CY+ATG transplantation preconditioning protocol. (2) According to the diagnosis of the disease, the transplantation pretreatment was designed: Patients with SAA-PNH syndrome or with PNH alone were treated with further modified BU/CY+ATG transplantation preconditioning protocol, and the BU dose was set as 9.6 mg/kg (intravenous drip in 3 days). Transplantation way: The "Beijing protocol" is use of bone marrow plus peripheral blood hematopoietic stem cell. Based on it, the protocol was modified to simple peripheral blood hematopoietic stem cell transplantation. Results 22 of 26 SAA patients underwent hematopoietic reconstruction. The patients were followed up until December 2019, and the results were as follows: During a median follow-up period of 48 (5-122) months, 5 patients died, 4 of whom suffered transplant-related deaths (15.4%, 4/26), and 1 of whom was due to central nervous system infection (3.8%, 1/26). The 3-year overall survival rate (OSR) was 84.2%, the 3-year progression-free survival (PFS) was 72.6% (SAA I: 100.0%, SAA-PNH: 100.0%, SAA II: 72.2%). Conclusions The further improved BU/CY+ATG transplantation preconditioning scheme is safe and effective in SAA with haploid peripheral blood stem cell transplantation. It is suitable not only for SAA I, SAA II, but also for patients with PNH clone, thus being worth wider clinical aplplication.

Decitabine-based conditioning regimen is feasible and effective in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia / 中华血液学杂志

Objective@#To assess the efficacy and toxicity of decitabine-based conditioning regimen in patients with myelodysplastic syndrome (MDS) , acute myeloid leukemia secondary to MDS (MDS-AML) or chronic myelomonocytic leukemia (CMML) .@*Methods@#From March 1, 2013 to May 25, 2015, 22 patients who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) with decitabine-based conditioning regimen were analyzed retrospectively.@*Results@#①22 patients, 14 males and 8 females with a median age of 42.5 (24-56) years old, were diagnosed as MDS (n=14) , CMML (n=4) , MDS-AML (n=4) . ②15 patients were treated with the conditioning regimen of decitabine combined with busulfan, cyclophosphamide, fludarabine, and cytarabine, the other 7 cases were treated with decitabine, busulfan, fludarabine, and cytarabine. The dose of decitabine was 20 mg·m-2·d-1 for 5 days.Rabbit anti-human anti-thymocyte globulin (2.5 mg·kg-1·d-1 for 4 days) was involved in conditioning regimen in patients with unrelated donor or haploidentical transplantation. ③Except 1 patient died of infection in 2 months after transplantation, the other patients were engrafted successfully. The median time of granulocyte engraftment was 13 (12-18) days, and the median time of platelet engraftment was 16 (13-81) days. ④The incidence of acute graft versus host disease (aGVHD) was (41.3±10.6) %, and severe aGVHD (grade of III-IV) was (18.4±9.7) %. The incidence of chronic graft versus host disease (cGVHD) was (56.4±11.3) %, and extensive cGVHD was (36.4±12.1) %. ⑤8 patients were suffered with cytomegalovirus (CMV) viremia. Among the 18 patients with definitely infection, 6 occurred during myelosuppression and 12 cases occurred after hematopoietic reconstruction. The 2-year and 3-year non-relapse mortality was (13.9±7.4) % and (24.3±9.5) %, respectively. ⑥The 2-year and 3-year overall survival (OS) was (77.3±8.9) % and (67.9±10.0) %, respectively. The 2-year and 3-year relapse-free survival (RFS) was (72.7±9.5) % and (63.6±10.3) %, respectively.@*Conclusions@#allo-HSCT with decitabine-based conditioning regimen is feasible in the treatment of MDS, MDS-AML or CMML.

Late chimerical status after bone marrow transplantation in severe aplastic anemia according to two different preparatory regimens

ABSTRACT Background: This study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. Methods: Patients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n = 55) received 200 mg/kg cyclophosphamide alone and Group II (n = 49) received 120 mg/kg cyclophosphamide associated with 12 mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. Results: Chimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51-90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value < 0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value = 0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value < 0.001) and higher number of infused cells (p-value = 0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value = 0.003) and platelet counts (p-value < 0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. Conclusion: These data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.

Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in autologous stem cell transplantation for newly diagnosed multiple myeloma

BACKGROUND: High-dose melphalan (HDMEL) represents the standard conditioning regimen before autologous stem cell transplant (ASCT) in multiple myeloma (MM), but recent updates have suggested combination of melphalan with bulsulfan (BUMEL) is also associated with favorable outcomes. We performed the current study to address the lack of comparative studies between the two conditioning regimens in Asian populations. METHODS: Using the Korean National Health Insurance and Korean Health Insurance Review and Assessment Service databases, 1,304 patients newly diagnosed with MM undergoing ASCT between January 2010 and December 2014 were identified. Patients were divided according to conditioning regimen (HDMEL vs. BUMEL), and after case matching, 428 patients undergoing HDMEL conditioning were compared to 107 patients undergoing BUMEL conditioning with respect to clinical course and treatment outcomes. RESULTS: The 3-year progression-free survival (PFS) was 52.5% for the HDMEL conditioning group versus 70.3% for the BUMEL conditioning group (P=0.043). The 3-year overall survival (OS) was 82.0% versus 83.5% (P=0.525), respectively. Although not statistically significant, BUMEL conditioning was associated with more platelet transfusion, while HDMEL was associated with more granulocyte colony stimulating factor support. In multivariate analysis, BUMEL conditioning was not inferior to HDMEL conditioning in regard to both PFS and OS. CONCLUSION: Our study confirmed that BUMEL is an effective and well-tolerated alternative to HDMEL conditioning, with better PFS.

Allogeneic hematopoietic stem cell transplantation for β-thalassemia major patients using a reduced-intensity conditioning regimen / 中华器官移植杂志

Objective To observe the efficacy and safety of reduced-intensity conditioning regimen used in allogeneic hematopoietic stem cell transplantation (HSCT) for children with β-thalassemia major.Methods We retrospectively analyzed the clinical data of 15 children with β-thalassemia major undergoing allogeneic HSCT with a reduced-intensity conditioning regimen from March 2013 to March 2017.Fifteen patients were diagnosed definitely,and the median age at transplantation was 5 years (range:3-6 years),including 11 with HSCT from unrelated donors (UDs),3 of HLA 8/10 matched and 8 of HLA10/10 matched.The remaining 4 patients out of 15 with HSCT were from related donors with HLA matched,3 donors were siblings and 1 was mother.All patients used a reduced-intensity conditioning regimen.The median mononuclear cell (MNC) dose and CD34 positive cell dose were 11.4 × 108/kg (range:4.8-20 × 108/kg)and 9.8 × 106/kg (range:5.9-27.2 × 106/kg),respectively.Graft-versus-host disease (GVHD) was prevented by cyclosporine A,methotrexate,MMF and ATGf.Results All 15 patients had successful engraftment.Median time to neutrophil and platelet engraftment was 12 days (range:9-21 days) and 15 days (range:10-25 days) respectively.Two patients developed grades Ⅱ acute GVHD and 4 patients developed chronic GVHD from unrelated donors,while there was no acute GVHD and 1 patient developed chronic GVHD from related donors.No patients suffered from serious transplantation-related complications,such as hepatic veno-occlusive disease (VOD),hemorrhagic cystitis,EB virus reactivation,CMV reactivation and hepatitis C,etc.The median follow-up time was 24 months (range:2-48 months).All patients were healthy and became transfusion-independent.Conclusion The reduced-intensity conditioning regimen proved to be safe and effective for children with β-thalassemia major given allogeneic HSCT.

Hot issues of hematopoietic stem cell transplantation in 39th Annual Meeting of the EBMT / 白血病·淋巴瘤

The 39th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT 2013) was held in London,UK from 7 to 10 April,2013.The meeting received more than 1000 submitted papers,covering leukemia,lymphoma,aplastic anemia,cellular and gene therapies and biology of graft-versus-host disease(GVHD).This review focuses on haploidentical hematopoietic stem cell transplantation (HSCT),improvements of conditioning regimen and early diagnosis and the management of GVHD.

Allogeneic hematopoietic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasms / 白血病·淋巴瘤

Objective To investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with intensified conditioning regimen followed by rapidly tapering immunosuppressants and sequential minimal residual disease (MRD)-guided donor lymphocyte infusion (DLI) post-transplantation on outcome of blastic plasmacytoid dendritic cell neoplasm (BPDCN).Methods Two cases of BPDCN from January 2009 to May 2011 in Nanfang hospital were diagnosed according to 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.Case 1 initially presented with typical cutaneous involvement and was promptly diagnosed with CD+4CD+56LCA+TdT+CD+43 BPDCN by skin biopsy.Case 2 was recognized as acute lymphocyte leukemia and acute non-lymphocytic leukemia,which was diagnosed to BPDCN at recurrence through flow cytometry analysis.Total-body-irradiation plus cyclophosphamide based intensified conditioning regimen were followed by allo-HSCT from sibling donor.Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate.Anti-thymocyteglobulin was included additionally for haploid donor allo-HSCT.Multi-color labeling flow cytometry was performed to monitor MRD.Rapidly tapering of prophylactic immunosuppressants and sequential MRD-guided donor lymphocyte infusion (DLI) were performed to control relapse of primary malignancy.Results Two cases of BPDCN received allo-HSCT from sibling donor after intensified conditioning regimen.Both patients achieved complete remission and complete donor engraftment.Case 1 survived refractory acyclovir-resistant Epstein-Barr virus viremia benefiting from preemptive treatment with rituximab and DLI-induced grade Ⅳ acute GVHD,but died of thrombotic microangiopathy mixed with diffuse alveolar hemorrhage and sepsis on +243 days.Case 2 relapsed just 2 months after allo-HSCT despite DLI and rapidly tapering of CsA,died of sepsis followed by diffuse intravascular coagulation on +101 days.Conclusion BPDCN is characterized with typical cutaneous and/or bone marrow involvement with CD4+CD+56CD+123CD+43 blastic plasmacytoid dendritic cell and highly aggressive clinical course.Allo-HSCT seems to be a promising treatment for early phase of aggressive BPDCN aided with MRD monitoring and DLI,but it deserves more intensive researches to promote outcome of advanced staged BPDCN.

O transplante de células-tronco hematopoéticas na leucemia linfoide crônica, uma proposta do I encontro de diretrizes do transplante de medula óssea da sociedade brasileira de transplante de medula óssea, Rio de Janeiro 2009 / Hematopoietic stem cell transplantation in chronic lymphoid leukemia: a proposal by the Brazilian consensus on bone marrow transplantation of the Brazilian society of bone marrow transplantation, Rio de Janeiro 2009

Portadores de leucemia linfoide crônica (LLC) apresentam curso clínico indolente e prolongado que devem ser diferenciados daqueles que têm doença de evolução agressiva e fatal. Pacientes mais jovens e com critérios de alto risco podem se beneficiar com tratamento mais agressivo como o transplante de células-tronco hemopoéticas (TCTH). O transplante autólogo apresenta casos com remissão citogenética e molecular, baixa taxa de mortalidade, mas não demonstram platô nas curvas de sobrevivência e alta taxa de recaídas. Os transplantes alogênicos com regime mieloablativos têm altos índices de toxicidade e mortalidade, mas evidenciam o efeito enxerto versus leucemia, que aumenta a possibilidade de cura destes indivíduos. Assim, a opção dos transplantes alogênicos está dirigida para os transplantes com regime de condicionamento não mieloablativo, que pode ser aplicado inclusive a pacientes mais idosos ou portadores de comorbidades, e manter o potencial efeito GVL. A identificação dos pacientes que podem ser beneficiados por esses procedimentos, caracterizar e apontar os novos marcadores prognósticos permanece objeto de muitos estudos clínicos e foi o objetivo do grupo responsável em discutir as diretrizes do TCTH no consenso da Sociedade Brasileira de Transplante de Medula Óssea - SBTMO. Assim, consideramos que o TCTH para a leucemia linfoide crônica (LLC) deve seguir, para sua indicação, os critérios do European Group for Blood and Marrow Transplantation (EBMT) e, quando houver disponibilidade de um doador aparentado, a opção deve ser do TCTH alogênico com regime não mieloablativo. O TCTH alogênico não aparentado e o autólogo devem ser considerados como opção secundária de indisponibilidade de doador, situações especiais e ensaios clínicos.

Patients with chronic lymphocytic leukemia usually have an indolent and prolonged clinical course and need to be differentiated from those who have an aggressive and fatal disease. Younger patients with high-risk criteria may benefit with a more aggressive treatment that includes hematopoietic stem cell transplantation (HSCT). Autologous transplantation, despite of the encouraging results with cases of molecular and/or cytogenetic remission and low mortality rates, does not present a plateau in survival curves and has a high relapse rate. Allogeneic transplantations using myeloablative regimens, have high toxicity and mortality rates, but also demonstrate the graft-versus-leukemia effect that increases the possibility of cure of these individuals. So the option of allogeneic transplants for patients with CLL is directed to conditioning using non-myeloablative regimens, which can also be applied to older patients or those with comorbidities, and maintain a potential graft-versus-leukemia effect. The identification of patients who may benefit from these procedures and the characterization of new prognostic markers remain the subjects of many clinical studies and were the objective of the group responsible for discussing guidelines for CLL of the consensus on HSCT SBTMO. Thus we believe that HSCT for CLL should follow the criteria of the EBMT. When a sibling donor is available the best option is allogeneic HSCT with a myeloablative regimen. The strategy of unrelated allogeneic or autologous HSCT must be considered as a second option when no donor is available, for special situations and clinical trials.

O transplante de células-tronco hematopoéticas como opção no tratamento de doenças não hematológicas: [revisão] / Hematopoietic stem cell transplant: a therapeutic option for non-hematologic diseases: [review]

Nesta revisão são abordadas as doenças em que existem dados e perspectivas do uso de transplante de células-tronco hematopoéticas em suas diversas modalidades. São apresentados também os aspectos referentes aos regimes de condicionamento empregados, e sua relação com toxicidade e taxa de mortalidade ligadas ao transplante. São apresentadas as doenças autoimunes e particularizados dados específicos do lúpus eritematoso sistêmico, esclerose sistêmica e esclerose múltipla e diabetes mellitus tipo 1. A base do procedimento nas doenças autoimunes é a reprogramação imunológica. Aparentemente o procedimento tem sua indicação nas doenças em que os tratamentos convencionais de imunossupressão tenham falhado, e o dano orgânico não tenha sido definitivo, mas tenha chance de ocorrer caso não seja realizado o transplante. A modalidade aparentemente indicada no momento deve ser o transplante de células-tronco autogênico com regimes de condicionamento não mieloablativo para se obter sobrevivência estimada em mais de 50 por cento em todas as doenças, com baixa toxicidade e com mortalidade nula ligada ao transplante. São apresentados também os resultados nos tumores sólidos, que são discutíveis, e particularidades no câncer de mama. A aparente indicação para os tumores sólidos é transplante de células-tronco alogênico e se baseia no tratamento intensivo com doses mieloablativas com a finalidade de se induzir o efeito enxerto contra o tumor. Os regimes não mieloablativos são preconizados com a finalidade de redução da toxicidade e indução de imunossupressão, sendo os dados insuficientes e discutíveis, o que obriga a introdução de novas estratégias terapêuticas baseadas na terapia imune e celular.

In this report we discuss data and perspectives of hematopoietic stem cell transplantation in non-hematologic diseases. Aspects related to the conditioning regimen and its relationship with toxicity and mortality are also presented. Specific autoimmune diseases are discussed, in particular systemic lupus erythematosus, systemic sclerosis, multiple sclerosis and type 1 diabetes mellitus. The aim of the procedure in autoimmune diseases is immune reprogramming. Apparently this procedure has indications for diseases in which conventional treatments have failed when organ damage is not definitive, but likely to occur if transplantation is not performed. The most promising method appears to be autologous stem cell transplantation with non-myeloablative conditioning regimens to obtain survival that is estimated at more than 50 percent for all autoimmune diseases, with low toxicity and no mortality related to transplantation. The controversial results of solid tumor treatment and particularities of breast cancer are also presented. Hematopoietic stem cell transplantation is the apparent indication for solid tumors based on intensive treatment with myeloablative doses in order to induce the graft versus tumor effect. The myeloablative conditioning regimens are introduced with the purpose of reducing the toxicity and inducing immunosuppression but the data are insufficient and questionable requiring the introduction of new therapeutic strategies based on cellular and immune therapy.

A retrospective compariso of cyclophosphamide plus antithymocyte globulin with cyclophosphamide plus busulfan as the conditioning regimen for severe aplastic anemia

Allogeneic hematopoietic stem cell transplantation (AHSCT) is the treatment of choice for young patients with severe aplastic anemia (SAA). The association of antithymocyte globulin (ATG) and cyclophosphamide (CY) is the most frequently used conditioning regimen for this disease. We performed this retrospective study in order to compare the outcomes of HLA-matched sibling donor AHSCT in 41 patients with SAA receiving cyclophosphamide plus ATG (ATG-CY, N = 17) or cyclophosphamide plus busulfan (BU-CY, N = 24). The substitution of BU for ATG was motivated by the high cost of ATG. There were no differences in the clinical features between the two groups, including age, gender, cytomegalovirus status, ABO match, interval between diagnosis and transplant, and number of total nucleated cells infused. No differences were observed in the time to neutrophil and platelet engraftment, or in the risk of veno-occlusive disease and hemorrhage. However, there was a higher risk of mucositis in the BU-CY group (71 vs 24 percent, P = 0.004). There were no differences in the incidence of neutrophil and platelet engraftment, acute and chronic graft-versus-host disease, and transplant-related mortality. There was a higher incidence of late rejection in the ATG-CY group (41 vs 4 percent, P = 0.009). Although the ATG-CY group had a longer follow-up (101 months) than the BU-CY group (67 months, P = 0.04), overall survival was similar between the groups (69 vs 58 percent, respectively, P = 0.32). We conclude that the association BU-CY is a feasible option to the conventional ATG-CY regimen in this population.

The clinical research of allogeneic hematopoietic stem cell transplantation using intravenous Bu/Flu conditioning regimen in the treatment of myeloid hematopathy / 中国实用内科杂志

20?109/L in 12 to 19(median 14)days after transplantation.Complete chimerism was achieved in all the patients at one month after HSCT.Two patients had acute GVHD and one had chronic GVHD.With a median follow-up of 31(19~37)months,8 of 9 patients were alive and disease-free.Conclusion The intravenous Bu/Flu conditioning regimen may reduce transplantation-related toxicities and can achieve full chimerism and high long-term disease-free survival.Allogeneic hematopoietic stem cell transplantation using intravenous Bu/Flu conditioning regimen is a safe and effective option for the patients with myeloid hematopathy.