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.

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.

scholarly journals What Is the Most Appropriate Source for Hematopoietic Stem Cell Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Itır Sirinoglu Demiriz ◽  
Emre Tekgunduz ◽  
Fevzi Altuntas
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source ◽  
Selection Of

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

scholarly journals An Encouraging Successful Result of Allogeneic Hematopoietic Stem Cell Transplantation in a Boy Both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta : A Case Report

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Fang Liu ◽  
Xiaofan Zhu ◽  
Wenyu Yang ◽  
Ye Guo ◽  
Xia Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Osteogenesis Imperfecta ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Juvenile Myelomonocytic Leukemia ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia

Background: Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in young children that is classified as a myelodysplastic/myeloproliferative neoplasm and not only characterized by young age, hepatosplenomegaly, thrombocytopenia and monocytosis, but also by molecular aberrations in the RAS-RAF-MEK-ERK signaling pathway and GM-CSF-hypersensitivity. Most children with JMML experience an aggressive clinical course and the only curative treatment option for these children is stem cell transplantation (SCT). Osteogenesis imperfect (OI) is also an orphan inherited monogenic bone fragility disorder that usually is caused by mutations in one of the two genes coding for collagen type I alpha chains, COL1A1 or COL1A2. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities. Current multidisciplinary management could only improve quality of life for patients, including physical therapy, drug treatment and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell or bone marrow transplantation, targeting the specific altered pathway rather than the symptoms, may develop new curative treatments. Here we report a 3-year-old boy who suffered from both JMML and OI, was successfully transplanted and kept presenting an encouraging outcome up to now. Aims:To investigate the possible efficacy and safety of Allogeneic Hematopoietic Stem Cell Transplantation in a boy both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta. Methods:A 3-year-old boy presented with fatigue, fever, petechia and rash in Aug 2019, accompanying with loss of appetite, joint pain and severe hepatosplenomegaly. The boy had a special appearance of short stature and blue sclerae, meanwhile he suffered intermittent eczema and bone fracture twice since he was 2 years old. Similar characteristics were also positive in his grandmother, father and father's sister. The blood cell counts revealed anemia, thrombocytopenia and leukocytosis especially monocytosis. Bone marrow aspirate showed excessive proliferation of myelomonocytic cells and hypersensitivity to granulocyte-macrophage colony-stimulating factor in vitro. Somatic mutation of gene NF1, PTPN11 and COL1A1 were identified by Next Generation Sequencing.Therefore, the little boy was diagnosed with two rare diseases of Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta at the same time. After 4 courses of hypomethylating agents therapy, the boy underwent haploidentical allogeneic bone marrow stem cell transplantation combined with allogeneic single umbilical cord blood transplant in May 2020. The myeloablative conditioning regimen was composed of Decitabine (20mg/m2/day, days -13 to -9), Cyclophosphamide (25mg/kg/day, days -8 and -7), Busulfan(100mg/m2/day, days -6 to -3), Fludarabine (40mg/m2/day, days -6 to -2) and Cytarabine (100mg/m2/day, days -6 to -2). Post-Cyclophosphamide (50mg/kg/day, days +3 and +4), tacrolimus and mycophenolate mofetil were used for prophylaxis of graft-versus-host disease (GVHD). Results:The number of infused TNCs from haplo-bone marrow and cord blood unit was 41.4×10^8/kg and 9.72×10^7/kg, respectively, while the number of infused CD34+ cells was 11.84×10^6/kg and 2.33×10^5/kg, respectively. The boy achieved sustained engraftment of both neutrophils and platelets at 16 days and 24 days, respectively, with complete haplo-donor chimerism of confirmed at 14 days. He developed grade III acute GVHD (skin, gut and liver) and recovered at 39 days after transplant. Clinical symptoms such as rash, joint pain and hepatosplenomegaly got complete remission, and the mutated genes like NF1, PTPN11 and COL1A1 all disappeared at 30 days. At the time of this report, the boy was alive with negative MRD and good quality of life with a follow-up of 3 months after HCT. Conclusion:To our knowledge, this is the first report that a child both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta was cured by allogeneic hematopoietic stem cell transplantation.Our experience suggests that allogeneic bone marrow transplantation may be a novel safe and effective therapeutic strategy for OI patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Morphological skin evaluation in the patients with systemic scleroderma before and after hematopoietic stem cell transplantation

2020 ◽  
Vol 9 (2) ◽  
pp. 60-66
Author(s):  
Galina V. Fedotovskikh ◽  
Galija M. Shaymardanova ◽  
Manarbek B. Askarov ◽  
Ainash A. Zhusupova ◽  
Natalya A. Krivoruchko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Effect ◽  
Hematopoietic Stem ◽  
Before And After ◽  
Autologous Hsct

Some promising clinical results of hematopoietic stem cell transplantation (HSCT) are reported in severe autoimmune diseases. When treating the patients with systemic scleroderma (SSD), histological evaluation of skin fibrosis includes scoring of myofibroblasts that are associated with excessive deposition of extracellular matrix components. The aim of our study was to evaluate morphological condition of skin in SSD patients before and after transplantation of autologous hematopoietic bone marrow stem cells. Patients and methods Twenty-eight patients were observed at the National Research Medical Center (Nur-Sultan), at the age of 45+11 years old (2 males, 26 females) with verified diagnosis of SSD according to ACR/EULAR (2013). Duration of the disease was 12+5.4 years old. Control group (12 persons) received conventional basic therapy Treatment protocol for the main group included autologous HSCT. Resistance to immunosuppressive therapy was a pre-requisite for HSCT. Bone marrow aspiration was performed from the iliac crest, the autologous mononuclear cells were isolated in Percoll density gradient and incubated for 72 hours at 37°С. Autologous HSCT was performed at a mean dose of 88×106 cells in 200 mL of physiological saline i/v over 3 hours. Clinical effect was evaluated by the recognized criteria (European Scleroderma Trials and Research Group, skin score by Rodnan). For morphological studies, the punch biopsies of tibial skin were taken in 15 patients before therapy, and in 9 three months after the treatment. The cellular therapy was accompanied by improved skin condition. The paraffin sections were stained with hematoxilin and eosin, as well as by Masson-trichrome technique. For electron microscopy, the skin biopsies were processed by conventional method, then being Epon-embedded. Semi-thin slices were stained with Methylene Blue, Azur II and basic fuchsine. For EM, the ultrathin sections were contrasted with uranyl acetate and lead citrate. Results Skin of SSD patients before treatment was characterized by induration and dystrophy and epithelial destruction, sclerosis and hyalinosis of dermal connective tissue, pathology of microcirculatory vessels. Ultrastructure of myofibroblasts in the sclerotized derma was characterized by functional overload. The active participants of fibrillogenesis were located in perivascular area, being represented by lymphocytes and fibroblasts of a specific SSD-specific population producing higher amounts of collagen and interstitial matrix. However, three months after HSCT, the main group of the patients exhibited a pronounced clinical effect with sufficient decrease of skin induration, reduced dysphagia, mitigation of muscle contractures, couping vasospasm attacks (Raynaud syndrome). Skin density was significantly decreased, with Rodnan scores changed from 12.9 to 8.7 (only 1-point decrease in the controls). HSCT promoted biodegradation of skin fibrotic tissue in SSD patients. The myofibroblasts were subjected to destruction, multiple and prolonged capillaries were observed, the cell composition of perivascular infiltrate shifted to normal state. Numerous phagocytic and secretory macrophages appeared, thus suggesting angiogenesis induction, tissue remodeling, regulation of fibroclast population, suppression of T- and B-lymphocytes playing an important role on SSD pathogenesis. Extensive telocyte connections presumed their participation in neoangiogenesis and transmission of regeneration signaling. Conclusion Transplantation of cultured autologous hematopoietic marrow stem cells in SSD patients promoted biodegradation of sclerotized dermal layer, as well as angiogenesis stimulation, restoration of epithelium and skin appendages 3 months after HSCT, thus corresponding to improvement of clinical symptoms.

Hepatocytes of Donor Origin in Recipients Liver, after Hematopoietic Stem Cell Transplantation in BetaThalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4063-4063
Author(s):  
Ardeshir Ghavamzadeh ◽  
Mehrzad Mirzania ◽  
Nahid Sedighi ◽  
Marjan Yaghmaie ◽  
Naser Kamalian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Beta Thalassemia ◽  
Hematopoietic Stem ◽  
Biopsy Specimens

Abstract Background Bone marrow and circulating stem cells contains stem cells with the potential to differentiate into mature cells of various organs. We determined whether stem cells transformed to hepathcytes. Methods Biopsy specimens from the liver were obtained from 11 patients who had undergone transplantation of hematopoietic stem cells from peripheral blood (8 patients) or bone marrow (3 patients). Four female patients had received transplants from a male donor and seven male patients had received transplants from a female donor.All patients had beta thalassemia major and fibrosis in biopsy specimens from the liver before hematopoietic stem-cell transplantation. Hematopoietic stem-cell engraftment was verified by short tandem repeat analysis. The biopsies were studied for the presence of donor-derived hepatocytes with the use of fluorescence in situ hybridization of interphase nuclei and immunohistochemical staining for CD45 (leukocyte common antigen), and a hepatocyte-specific antigen. Results All 11 recipients of sex-mismatched transplants showed evidence of complete hematopoietic donor chimerism. XY-positive hepatocytes accounted for 4 to 6.7 percent of the cells in histologic sections of the biopsy specimens of female patients. These cells were detected in liver tissue as early as 1 year and as late as 8.5 year after the hematopoietic stem cell transplantation. Conclusions Bone marrow and circulating stem cells can differentiate into mature hepatocytes in beta thalassemia major patients who undergone hematopoietic stem cell transplantation.

Defining the Development of Receptive Niches for in Utero Transplantation of Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3527-3527
Author(s):  
Christine Michelle Jeanblanc ◽  
Evan Colletti ◽  
Christopher D Porada ◽  
Graca Almeida-Porada ◽  
Esmail D. Zanjani
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
In Utero ◽  
Immune Competence ◽  
Hematopoietic Stem ◽  
Sheep Fetus

Abstract Abstract 3527 Poster Board III-464 In utero hematopoietic stem cell transplantation (IUSCT) is a promising therapeutic alternative to postnatal stem cell transplantation which could potentially provide successful treatment for many genetic and developmental diseases affecting the immune and hematopoietic systems. Advances in molecular biological techniques and improvements in obstetrical procedures such as chorionic villous sampling now permit the collection of fetal material and the diagnosis of genetic disorders early enough in gestation to allow the use of IUSCT to treat these diseases prior to the onset of irreversible organ damage. However, after almost 20 years of experimental work, the only clinical applications for which IUSCT has proven successful are diseases such as SCID in which there is a selective advantage of donor cell development over host cells. Thus, the future success of this promising approach depends upon a full understanding of the mechanisms of engraftment and differentiation of stem cells during the fetal period. The sheep fetus shares many important immuno-physiological and developmental characteristics with the human fetus and has served as an accurate model in which to study IUSCT. Therefore, in the present studies we used the sheep model to evaluate the evolution and maturation of the microenvironmental niches during fetal development with the goal of delineating the period of gestation during which a multilineage-supporting bone marrow environment is present. To achieve this objective, we performed histologic and immunofluorescence analyses on bone from fetal sheep at 5.7, 6.5, 7.2, and 9.2 gestational weeks (gw; term: 21 gw), using antibodies to markers expressed on various niche cells. At the earliest time point of 5.7gw, the bone rudiment consisted mainly of mesenchymal structures, and no cells expressing markers of endothelium (CD34, CD31) or osteoblasts (osteopontin, N-cadherin) were observed. Beginning at 6.5gw, an extremely limited number of osteoblasts were present, possibly indicating the onset of development of the osteoblastic niche at that point. Cells exhibiting a CD34+ALDH+ phenotype were also observed in specific areas lining the perichondrium and within some endochondral compartments. Larger numbers of osteoblasts were seen at 7.2gw, and this was the first point at which we began to observe the association of CD34+ALDH+ cells with these bone niches. By 9.2gw, the population of osteoblasts was well established and the population of CD34+ALDH+ cells closely interacted with the osteoblasts, suggesting that the osteoblastic niche began forming at 6.5gw, but only became fully established by 9.2gw. When similar analyses were performed with antibodies to CD34 and CD31 to detect endothelial cells, we found that CD34+CD31+ endothelial cells were not present in detectable numbers at 5.7, 6.5, or 7.2gw, but by 9.2gw, the CD34+CD31+ population had increased dramatically, indicating that the vascular niche develops fairly rapidly during between 7.2 and 9.2gw in the sheep. These data collectively indicate that the bone marrow osteoblastic niche commences development at 7.2gw and reaches relative maturity by 9.2gw, while the vascular niche develops relatively rapidly between 7.2 and 9.2gw. These findings have important implications for optimizing engraftment of HSC following transplantation in utero and may help to explain the limited clinical success that has thus far been achieved with this approach. Given that the sheep fetus begins to attain immune competence at around 9.2gw, we routinely perform IUSCT between 7.8-8.6gw to avoid potential complications associated with immune rejection of the transplanted HSC. Based on our present results, it appears that in so doing, we are actually transplanting the HSC at a time when neither the osteoblastic or vascular niches have fully developed, making it unlikely they can serve as receptive sites for engraftment of the transplanted HSC. In the light of these findings, it is thus crucial to further narrow down the window of development of both the vascular and osteoblastic niches to determine the precise developmental time for optimal HSC engraftment. Given that our present results suggest this may be near the time the fetus achieves immune-competence, future strategies for improving the success of IUSCT may need to incorporate immuno-modulation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Some clinical lessons from one Blood and Marrow Transplantation Unit in Medellin, Colombia

JBMTCT ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. p102
Author(s):  
Francisco CUELLAR-AMBROSI ◽  
Mónica Monsalve Moreno MD ◽  
Beatriz Urrego Grisales ◽  
Jorge Cuervo Sierra ◽  
Guillermo Gaviria Cardona ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Bone Marrow Transplant ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Blood And Marrow Transplantation

After more than 60 years of the first successful bone marrow transplant (BMT) by D.E. Thomas for the treatment of hematological malignant diseases and more than 46 years since the first bone marrow transplant by Alberto Restrepo-Mesa in Medellin-Colombia for the treatment of a female triplet patient with paroxysmal nocturnal hemoglobinuria and aplastic anemia, in Colombia only around 750 bone marrow transplants are performed annually. With the experience accumulated during these years by each one of us, the León XIII Clinic of the Universidad de Antioquia began the hematopoietic stem cell transplantation (HSCT) program for adults in 2014. In this review, we report some clinical lessons drawn from the different phases of the HSCT in 109 adult patients with hematological malignancies. The progression-free survival (PFS) and the five-year overall survival (OS) were for autologous stem cell transplantation (ASCT) (87% and 70%), allogeneic stem cell transplantation (Allo SCT) (50% and 40%) and haploidentical stem cell transplantation (Haplo SCT) (25% and 18%) respectively.

Sign in / Sign up

Export Citation Format

Share Document