Clinical Outcomes and the Impact of Anti-Thymocyte Globulin (ATG) and Chronic Graft Versus Host Disease (cGVHD) Following Pediatric Allogeneic Stem Cell Transplantation: A Comparison between Peripheral Blood and Bone Marrow as a Source of Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1809-1809
Author(s):  
Parneet Cheema ◽  
Sunil Desai ◽  
Ronald Anderson ◽  
Max Coppes ◽  
Victor A. Lewis
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Allogeneic Bone ◽  
The Impact

Abstract INTRODUCTION: The use of peripheral blood as a source of stem cells for pediatric allogeneic stem cell transplantation remains controversial. We present a retrospective analysis evaluating the safety and efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) compared to allogeneic bone marrow transplantation (BMT) for the treatment of acute leukemia at our centre. The impact of ATG added to the treatment regimen was also evaluated in this analysis. METHODS: A chart review was conducted on all pediatric patients who underwent an allogeneic stem cell transplant for acute leukemia between April 1991 and August 2003 at the Alberta Children’s Hospital. All patients who received stem cells from HLA matched or one-antigen mismatched donors were included in this analysis. Data were analyzed using SPSS. RESULTS: 85 children (ages 9 months to 17 years) met study criteria. 24 patients underwent a PBSCT while 61 patients, a BMT for the treatment of either ALL (n=54) or AML/MDS (n=31). Median follow up time was 5.9 years. Six of 24 patients in the PBSCT group, and 30 of the 61 patients in the BMT group received ATG (p=.042). There was a trend towards increased overall survival (OS) at 5 years following PBSCT (p=.078). Disease free survival (DFS) at 5 years following PBSCT and BMT was similar (p=.297). Subgroup analysis found no difference in OS or DFS between PBSCT and BMT in patients receiving (p=.221, p=.820) or not receiving ATG as part of the conditioning regimen (p=.448, p=.820). Chronic GVHD was increased following PBSCT (45.8%) compared to BMT (19.7%) (p=.015). The rate of severe cGVHD, however, was not significantly different (25% vs. 11.5% for PBSCT and BMT, p=.119) between the two groups. No patients receiving ATG prior to PBSCT developed cGVHD (p=.009). Addition of ATG to the transplant regimen had no impact on the rate of cGVHD following BMT (p=.221). There was no increase in mortality due to cGVHD following PBSCT (p=.243) or BMT (p=.865). Although, there was a trend to improved DFS in patients who developed cGVHD following PBSCT, this was not statistically significant (p=.057). Despite a statistically significant increase in TRM found in all patients with cGVHD at one year post-transplantation (p=.048), there was no difference in TRM between the PBSCT (4.2%) and BMT (14.8%) groups (p=.173). CONCLUSION: Allogeneic PBSCT is a safe and effective alternative to allogeneic BMT for the treatment of acute leukemia in the pediatric population. Although there is an increased rate of cGVHD following PBSCT this does not appear to influence OS, DFS or TRM in our analysis. Addition of ATG into the transplant regimen decreases the occurrence of cGVHD after PBSCT. Studies to further assess the role of ATG in PBSCT are warranted.

The Outcome of Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukaemia: A Single Centre 10-Year-Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4515-4515
Author(s):  
Patrycja Zielinska ◽  
Malgorzata Krawczyk-Kulis ◽  
Miroslaw Markiewicz ◽  
Monika Dzierzak-Mietla ◽  
Anna Koclega ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Cumulative Probability

Abstract Abstract 4515 Chronic lymphocytic leukemia (CLL) is an incurable disease when treated with standard chemotherapy. The only possibility to provide cure is allogeneic stem cell transplantation (allo-SCT). CLL patients aged less than 55 account for about 15% of patients and these cases allo-SCT should be taken into consideration. The indications for allo-SCT are as follows: del17p, resistance to chemoimmunotherapy, Richter’s syndrome or recurrent disease. A retrospective analysis of allo-SCT in 18 patients (10 males, 8 females) with CLL transplanted in years 2000–2010 was performed. The aim of the study was to assess of long term follow-up outcome of allo-SCT in CLL patients. The median age at diagnosis was 41ys (range: 35–51). The sibling donor was available in 16 cases (2 pts were mismatched), unrelated donors were in 2 cases (1 mismatched). Most of the pts (16 out of 18) were MRD positive when allotransplanted. Median lymphocytosis preceeding allo-SCT was 5.9G/l. Peripheral blood was the source of stem cells in 9 cases (50%), and bone marrow in the remaining 9 cases, 2 pts were transplanted with stem cells from bone marrow and peripheral blood. 4 pts (22%) underwent the allograft procedure twice or more. Reduced intensity conditioning with alemtuzumab was performed in 9 pts (50%), myeloablative regimen in 4 cases and RIC with rituximab in one case.The median number of CD34+cellsx10^6/kg was 4.1 (range: 0.86–9.64). All but one patient engrafted (this pt was transplanted again successfully in one year time). Acute graft-versus host disease (GvHD) was noted in 46% of pts (only in 2 pts grade IV). Extensive GvHD was observed only in 2 pts. Donor lymphocyte infusion (DLI) was performed in 8 pts (44%). With a median follow-up of 73 months (range: 9–89) for surviving patients, the five-year Kaplan-Meier of overall survival (OS) and progression free survival (PFS) was 55,5% and 34%, respectively. At five years, the cumulative probability of non-relapse mortality was 15%. Allogeneic stem cell transplantation remains the effective treatment in CLL for selected group of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Beginning of a Journey of Autologous Stem Cell Transplantation in Combined Military Hospital, Dhaka, Bangladesh

2018 ◽  
Vol 8 (2) ◽  
pp. 177-180
Author(s):  
Mohammed Mosleh Uddin ◽  
Huque Mahfuz ◽  
Md Mostafil Karim
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Haematopoietic Stem Cell ◽  
Military Hospital

Haematopoietic stem cell transplantation (HSCT) involves the intravenous infusion of autologous or allogenic stem cells collected from bone marrow, peripheral blood or umbilical cord to re-establish haematopoietic function in patients whose bone marrow or immune system is damaged or defective. HSCT are mainly of two types –autologous stem cell transplantation (SCT) and allogenic SCT. Autologous SCT is mainly performed in multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma and less commonly in acute myeloid leukaemia. Haematopoietic stem cells are mobilized from bone marrow to the peripheral blood after the use of mobilizing agents, granulocyte colony stimulating factor (G-CSF) and plerixafor. Then the mobilized stem cells are collected from peripheral blood by apheresis and cryo-preserved. The patient is prepared by giving conditioning regimen (high dose melphelan). Stem cells, which are already collected, are re-infused into patient’s circulation by a blood transfusion set. Engraftment happens 7-14 days after auto SCT. Common side effects of this procedure include nausea, vomiting, diarrhoea, mucositis, infections etc. The first case of SCT performed in Combined Military Hospital, Dhaka, Bangladesh is presented here.Birdem Med J 2018; 8(2): 177-180

Multiple Myeloma Patients Treated with Allogeneic Stem Cell Transplantation Show an Increased Frequency of Bone Marrow-Residing CD4+Foxp3+ T Regulatory Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5206-5206
Author(s):  
Djordje Atanackovic ◽  
Yanran Cao ◽  
Christiane Faltz ◽  
Katrin Bartels ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Regulatory Cells

Abstract BACKGROUND: Immunosuppressive CD4+Foxp3+ T regulatory cells (Treg) play a vital role in immune regulation. Thus, Treg contribute to the prevention of autoimmune disease and graft-versus-host reactions following allogeneic stem cell transplantation (alloSCT) but also to the inhibition of effective anti-tumor T cell responses. It has previously been suggested that the frequency of Treg is increased in the peripheral blood of patients with multiple myeloma (MM). However, little is known about the presence of Treg in the bone marrow and it is unclear whether allogeneic stem cell transplantation might deplete Treg from this immune compartment. METHODS: In the present study, we analyzed percentages of CD4+Foxp3+ Treg as well as Treg expression of CD45RA and CCR7 in the bone marrow (BM) and in the peripheral blood of MM patients who had received alloSCT (N=42), in newly diagnosed MM patients (N=18), and in healthy controls (N=15) using flow cytometry. In addition, we performed inhibition assays in order to test the functional relevance of peripheral and BM-residing Treg. RESULTS: While newly diagnosed MM patients and healthy controls showed no significant difference in the proportions of CD4+Foxp3+ Treg in the bone marrow, percentages of BM-residing CD4+Foxp3+ T regulatory cells were markedly higher (p<0.001 and p<0.01) in patients post alloSCT (3.3±0.3%) than in normal BM (1.0±0.3%) or in BM of untreated MM patients (1.8±0.4%). In both groups of patients (p<0.05) as well as in the healthy controls (p<0.001) percentages of Treg were higher in the peripheral blood than in the bone marrow. While there were no differences regarding the percentages of peripheral Treg between the remaining groups, patients post alloSCT had higher percentages of peripheral Treg than newly diagnosed patients (5.6±0.8 vs. 3.2±0.7%, p<0.05). More than 90% of these donor-derived peripheral and BM-residing Treg expressed a memory T cell phenotype, being negative for CD45RA and CCR7. Importantly, peripheral as well as BM-residing Treg of patients post alloSCT were capable of inhibiting the proliferation of autologous non-Treg CD4+ T cells. CONCLUSION: Our study demonstrates for the first time an increased frequency of immunosuppressive Treg in the bone marrow of MM patients. Remarkably, in our patients these memory-type Treg were all donor-derived and led to an efficient replenishment of Treg in the periphery. These Treg might be necessary for the prevention of graft-versus-host disease in the transplanted MM patients, however, they might also contribute to the failure of an effective graft-versus-myeloma effect in the majority of the patients.

Haplo-Identical Allogeneic Stem Cell Transplantation Using GCSF-Mobilized Marrow Plus Blood Stem Cells from Parent Donors for Children with High-Risk Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5084-5084
Author(s):  
Quanyi Lu ◽  
Xiaoqing Niu ◽  
Peng Zhang ◽  
Delong Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells

Abstract Increasing number of patients in China have difficulty of finding sibling donors due to limited number of siblings. We therefore explored the feasibility using haploidentical parent donors for allogeneic hematopoietic stem cell transplantation. Eight leukemia patients were studied in our hospital. These included 2 CML-BC, 2 MDS-RAEB, 3 relapsed ALL and 1 relapsed AML. The median age was 12 (7–17). GCSF- mobilized bone marrow and peripheral blood stem cells were collected from parents (1 to 3 locus mismatched). The conditioning regimen consisted of fludarabine (30mg/m2/d x5), bulsulfan (4mg/kg/d x3) and cyclophosphamide (50mg/kg/d x2). Cyclosporin A, mycophenolate mofetil, methotrexate, and ATG were used for GVHD prophylaxis. The total number of CD34+ cell in the grafts ranged between 5–10 x 106/kg. The median follow- up was 13 months (6–24). One patient failed to engraft, the other 7 patients achieved full donor chimerism at day 28. The incidence of acute GVHD (grade II-IV) was 57.1% (4 of 7). The incidence of chronic GVHD of limited stage occurred in the same 4 patients. One patient died of lung complication at 17th month, another patient with CML-BC relapsed 10 months after transplantation. The rest 6 patients are alive without disease. These results suggested that parents could be considered as stem cell donors in the absence of alternative donors for young patients with high-risk diseases. GCSF-primed bone marrow plus peripheral blood stem cells might be beneficial to reduce the risk of GVHD for leukemia children in China. More patients are needed to further study this approach.

Clinical Characteristics and Outcome of Isolated Extramedullary Relapse in Acute Leukemia Following Allogeneic Stem Cell Transplantation: A Single Institutional Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4211-4211
Author(s):  
Jimin Shi ◽  
Xiaojian Meng ◽  
Yi Luo ◽  
Yamin Tan ◽  
Xiaoli Zhu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Bone Marrow Involvement ◽  
Molecular Abnormalities ◽  
Extramedullary Relapse

Abstract Abstract 4211 Isolated extramedullary relapse (EMR) of acute leukemia (AL) is a rare occurrence although it appears to be more common following allogeneic stem cell transplantation (allo-SCT). To characterize what has been observed in isolated EMR, we investigated a total of 287 consecutive AL patients (144 acute myeloid leukemia, 138 acute lymphocytic leukemia and 5 acute mixed lineage leukemia) who underwent allo-SCT. Forty-seven (16.4%) patients experienced relapse after allo-SCT. 12 cases (4.2%) experienced relapse of extramedullary sites without concomitant bone marrow involvement. Isolated EMR accounted for 25.5% of the overall initial relapse. The time to relapse after allo-SCT was longer in the extramedullary sites than in the marrow (median, 10 months vs. 5.5 months, P<0.05,). Sites of EMR varied widely including central nervous system, skin, bone, pelvis and breasts. The variables considered for univariate analysis included donor gender, age, primary disease, disease status, cytogenetics/molecular abnormalities, preconditioning regimen, donor type, HLA match, aGVHD and cGVHD. The variables that showed significant correlation with isolated EMR were the cytogenetics abnormalities at diagnosis. The prognosis for patients who develop EMR remained poor but was relatively better than that after bone marrow (BM) relapse (overall survival, 10 vs. 18 months, P<0.05). Compared with local or single therapy, patients treated with systemic in combination with local treatment could yield favorable prognosis. Three patients survived 63, 55 and 49 months after transplant respectively, of whom two received DLI with subsequent chemotherapy and (or) irradiation and one had surgery with subsequent chemotherapy. In conclusion, we observed a significant number of isolated EMR of AL after allo-SCT and intensive approaches combined of local and systemic therapy can produce favorable response which may cure a percentage of these patients. Disclosures: No relevant conflicts of interest to declare.

Autologous Hematopoetic Stem Cell Transplantation as An Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4595-4595
Author(s):  
Sonja G Genadieva-Stavrik ◽  
Alexandra Pivkova ◽  
Zlate Stojanoski ◽  
Svetlana Krstevska-Balkanov ◽  
Borce Georgievski
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Transplantation ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Source

Abstract Abstract 4595 Despite advances in our understanding of its pathogenesis, acute myeloblastic leukemia remains difficult to treat. Although initial complete remission can be achieved in a high percentage of patients, relapse occurs in 70–80% of the patients. Two main approaches have been the attempt to eradicate the leukemic clonal cells population via chemotherapy with or without autologous stem cell rescue or to pursue a combined approach using an antileukemic therapy combined with an antileukemic immune response via allogeneic bone marrow transplantation. Autologous transplantation compares favorably against allogeneic bone marrow transplant in several ways. Autologous transplantation can be used as a consolidation therapy in the older population, and lack of a matched donor does not preclude the patients from this treatment. We report a retrospective analysis on 48 patients diagnosed with de novo AML, who did not have an available histocompatible donor, and who underwent autologous transplantation between years 2000–2009 at the University hematology Clinic, Skopje, Macedonia. All patients had ECOG score 1 or less. The patient's age ranged from 17 to 65 years with the median age 41 years. There were 26 males and 22 females. For stem cell mobilization patients received chemotherapy or chemotherapy plus G-CSF. The preparative chemotherapy regimen prior to autologous transplantation consisted of BuCy in 24 patient, BEAM in 22 and BuCyMel was used in the remaining 2 patients. We used bone marrow as primary source of stem cells in 18 patients, and peripheral blood stem cells in remaining 30 patients. The five years overall survival was 52% and the 5 years disease progression free survival were 42%. We analyzed sever factors that can influence the overall survival and the disease free survival such as: age, disease status, stem cell source, chemotherapy regiments prior to transplantation, conditioning regiments, number of mobilized stem cells. Advanced age and bone marrow stem cell source seems to be more influent factors. We report that the clinical results of autologous hematopoietic stem cell transplantation are sufficiently encouraging to warrant future trials that include autologous transplantation as an option for appropriately selected patients with AML in CR1. We conclude that autologous hematopoietic stem cell transplantation is a reasonable and save intensive consolidation for patients with acute myeloblastic leukemia who do not have a suitable HLA–matched donor. Disclosures: No relevant conflicts of interest to declare.

The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4185-4185
Author(s):  
Koji Kato ◽  
Yoshiko Atsuta ◽  
Kazuteru Ohashi ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Sources ◽  
The Impact

Abstract Abstract 4185 Background: Since the clinical implication of anti-lymphocyte globulin (ATG/ALG) in allogeneic stem cell transplantation (allo-SCT) is not fully understood, we tried to identify the clinical impact of ATG/ALG in patients with acute leukemia who received allo-SCT in Japan. Patients and Methods: We analyzed patients with ALL (n=5494) and AML (n=8115) who received first allogeneic SCT from 1983 to 2009 with (n=356) or without (n=13253) ATG/ALG. Their stem cell sources were bone marrow (BM, n=9056), peripheral blood (PB, n=1918), and cord blood (CB, n=2575) and they were transplanted at 1st complete remission (CR1, n=5681), 2nd CR (CR2, n=2495), and advanced stages (>CR3, n=5033). Results: Five year overall survival (5y OS) of all patients with or without ATG/ALG was 33.6% vs 44.5%, respectively (P<0.001) and multivariate analysis showed that ATG/ALG significantly reduced acute GVHD (P<0.001, HR=1.980) as well as chronic GVHD (P<0.001, HR=1.894). According to stem cell sources, 5y OS with or without ATG/ALG was 35.8% vs 47.5% (P<0.001) in BM, 34.7% vs 37.6% (P=0.067) in PB and 18.3% vs 39.9% (P<0.001) in CB. By multivariate analysis, ATG/ALG significantly reduced A-GVHD (P=0.005, HR=1.565) but decreased OS (P=0.004, HR=0.729) in BM, it reduced A-GVHD (P<0.001, HR=2.376) and C-GVHD (P<0.001, HR=2.691) but lowered engraftment (P=0.046, HR=0.810) in PB, and it increased TRM (P=0.004, HR=0.437) with decreased OS (P=0.011, HR=0.576) in CB. In Haplo transplantation (SCT from 2 or 3 antigens of HLA mismatched family donor, n=337), multivariate analysis showed that ATG/ALG did not affect the relapse, TRM and OS but, it significantly lowered engraftment (P=0.002, HR=0.602), and reduced A-GVHD (P<0.001, HR=2.622) as well as C-GVHD (P<0.001, HR=3.834). In contrast to these results, ATG/ALG did not affect the relapse rate irrespective of stem cell source or diagnosis. Conclusion: In allogeneic stem cell transplantation for patients with ALL and AML, ATG/ALG contribute in reducing acute and chronic GVHD without affecting relapse rates but it was a risk factor of OS for patients who received BM or CB. Disclosures: No relevant conflicts of interest to declare.

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