Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated EMR in the CNS is a relatively rare form of recurrent leukemia. We report here a case of a 38-year-old man with inv(16) acute myeloid leukemia (AML, M2) who suffered a central nervous system (CNS) relapse after allogeneic bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling donor. After complete remission was achieved by chemotherapy, he received allogeneic BMT from his HLA-matched sister. His leukemia relapsed in the CNS 2.5 years after the allogeneic BMT. Lumbar puncture revealed 780/muL white blood cells with 67.3% leukemia cells and 32.7% mature lymphocytes. Fluorescent in situ hybridization (FISH) using a probe for the Y chromosome demonstrated that both leukemia cells and lymphocytes in the cerebrospinal fluid (CSF) were derived from the recipient, although the bone marrow cells were from the donor. No leukemia cells with inv(16) were detected by FISH in the bone marrow. This is the first report to clarify the chimerism of lymphocytes in the CSF of patients with isolated EMR in the CNS after allogeneic SCT, in which analysis revealed that autologous immunologic cells rather than donor lymphocytes responded to the recurrent isolated leukemic cells in CNS. This observation suggests that the CNS is a "sanctuary" site not only from chemotherapy but also from the graft-versus-leukemia effect. The present case contributes to our understanding of the possibility of immunological escape phenomenon of recurrent leukemia cells in extramedullary sites.
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PMID:Isolated extramedullary relapse presenting as autologous lymphocyte response. 1830 63

This study aimed to identify which graft product subset of CD34+ cells might be the most predictive of early hematopoietic recovery following allogeneic peripheral SCT (allo-PBSCT). The relationship between the number of 'mature' subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD133-) and 'immature' subsets of CD34+ cells (CD34+/CD33-, CD34+/CD38-, CD34+/DR- and CD34+/CD133+) and early neutrophil and platelet engraftment were studied in a homogeneous series (for disease, pre transplant chemotherapy, conditioning regimen and GVHD prophylaxis) of 30 AML patients after allo-PBSCT from HLA-identical siblings. In our experience, the total CD34+/CD133+ cell number was inversely correlated with the days required for the recovery of 0.5 x 10(9)/l neutrophils (r=or-0.82, P=0.02) and platelets of 20 x 10(9)/l (r=or-0.60, P=0.06); this correlation was better than the total CD34+ cell dose and neutrophil (r=or-0.70, P=0.04) and platelet engraftment (r=or-0.56, P=0.07). We suggest that a high number of CD34+/CD133+ PBSC may be associated with faster neutrophil and platelet recovery; these findings may help to predict the repopulating capacity of PBSC in patients after allo-PBSCT, especially when a relatively low number of CD34+ cells is infused.
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PMID:Subsets of CD34+ and early engraftment kinetics in allogeneic peripheral SCT for AML. 1842 47

SCN is characterized by neutropenia, life-threatening infections, and progression to myelodysplastic syndrome/acute myelogenous leukemia. The only curative option is SCT, but few reports using UCB as a stem cell source exist. Here, we report two SCN patients transplanted with UCB. Patient 1 was transplanted at seven yr of age due to increasingly large injections of G-CSF (>100 microg/kg/day) and the risk of developing leukemia. He engrafted promptly and is clinically well and immune reconstituted >2 yr post-transplant. Patient 2 underwent UCB SCT at nine months of age for recurrent severe infections, despite high doses of G-CSF. He rejected his first graft, having 100% host cells on day +35, and immediately underwent a second UCB SCT. He engrafted but experienced late graft rejection six months after the second transplant. He received a third UCB SCT following a more immunosuppressive conditioning regimen. His course was complicated by HHV-6 viremia and gut GVHD, but he is now clinically well and has 99% donor engraftment >20 months post-transplant. We conclude that UCB is an acceptable stem cell source for SCN patients, but conditioning must be adequately immunosuppressive to ensure engraftment in patients without prior chemotherapy.
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PMID:Unrelated cord blood transplantation for severe congenital neutropenia: report of two cases with very different transplant courses. 1843 8

To control severe GvHD while maintaining strong GvL effects in the context of allo-stem cell transplantation (allo-SCT), a phase I/II clinical trial of infusions of donor lymphocytes transduced with the herpes simplex virus thymidine kinase (TK-DLI) started at the Tsukuba University Hospital. To date, five (2 AML, 2 ALL, and 1 MDS) out of eight patients enrolled in the trial received approximately 7x10(7) transduced cells per kilogram of body weight and four patients showed some clinical responses such inhibition of the leukemic cell proliferation or mitigation of lymph node swelling. Especially, one MDS patient achieved complete remission and has remained in CR for 2 years after the treatment. GvHD developed in two patients (1 acute and 1 chronic) and the acute (grade III) was successfully controlled by administration of ganciclovir without any immunosuppressive drugs. Since HSV-TK as a strong antigen induced CTLs against transduced cells in patients, however, TK-DLI is expected to provide a more effective adoptive immune cell therapy by performance just after allo-SCT where the patient's immune function is severely damaged.
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PMID:Gene and cell therapy for relapsed leukemia after allo-stem cell transplantation. 1850 42

We report successful outcome in 13 children (median age 2.2 years) with high-risk AML who received SCT from an unrelated (11) or identical sibling (2) donor after a preparative regimen consisting of BU, CY and melphalan. Three children were 'poor'-risk in first CR, three in the second CR, five in PR and two had resistant disease. Immunotherapeutic strategies were employed to maximize a GVL response escalating through a reduced dose of alemtuzumab, early taper of CsA, donor lymphocyte infusion and treatment with alpha-IFN. Ten out of 13 (77%) children are alive in CR at a median of 41 months (range: 17-88) from SCT. There was no TRM, but three children relapsed and died 3, 4 and 17 months after SCT. These encouraging early results warrant further studies in children with very high-risk AML.
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PMID:Successful outcome of allo-SCT in high-risk pediatric AML using chemotherapy-only conditioning and post transplant immunotherapy. 1856 Apr 12

Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by real-time PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.
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PMID:Minimal residual disease diagnostics in myeloid malignancies in the post transplant period. 1858 31

Allogeneic hematopoietic SCT (HSCT) for children with standard-risk AML in first CR (CR1) is controversial. We reviewed 32 consecutive children with standard-risk AML who received matched sibling donor HSCT in CR1 from 1995 to 2004. With a median follow-up of 76 months (range: 36-114), 3 year EFS was 0.74 (95% confidence interval (CI): 0.57-0.88) and the overall survival was 0.81 (95% CI: 0.66-0.93). Only one patient died as a result of TRM. Larger studies, such as the MRC-UK 10 and 12, reported 60-62% EFS. Outcome of children with standard-risk AML transplanted from a matched sibling donor in CR1 is very encouraging with minimal toxicity.
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PMID:Pediatric standard-risk AML with fully matched sibling donors: to transplant in first CR or not? 1858 34

Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.
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PMID:Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML. 1867 72

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.
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PMID:The stem cell transplant program in Pakistan--the first decade. 1872 82

In Vietnam, the first three cases of Allo-BMT were successfully performed in 1995 at the Blood Transfusion and Hematology Hospital (BT-H) of Ho Chi Minh City. Donors were HLA fully matched siblings (HLA-A, HLA-B and HLA-DRB1). The patients were a 26-year-old man with CML in chronic phase (CP), a 12-year-old woman with beta-thalassemia/Hb E and a 9-year-old girl with beta-thalassemia/Hb E. All patients were engrafted with the median time to recover ANC>0.5 x 10(9)/l, and platelet count >20 x 10(9)/l was 16 and 38 days. At 12 years after transplantation, all three patients are alive and well. Today, Vietnam has five SCT centers; in the north, there are three centers: 108 Military Hospital, Pediatric Institute and Blood transfusion and Hematology Institute; in the middle of Vietnam is Hue Hospital and in the south, the BT-H Hospital of Ho Chi Minh City. Until now, 65 patients have had SCT in Vietnam; among them, 52 patients had SCT at the BT-H Hospital, Ho Chi Minh City. Because of no connection of data between different SCT centers, we present here only the results performed at the BT-H Hospital, Ho Chi Minh City. With Allo-SCT we performed 19 cases with 3 procedures: BMT (4 cases), PBSC (6 cases) and cord blood transplantation (9 cases); patients were diagnosed with AML (n=7), ALL (n=1), CML (n=5) and beta-thalassemia (n=6). Following transplantation, 7 patients (36.84%) relapsed, 12 (63.16%) remained alive and overall survival times: 6.81+/-1.35 years, disease-free survival times: 6.69+/-1.4 years (range 0.5-12 years). With Auto-SCT: since November 1996, we have performed 33 cases of autologous PBSC transplantation consisting of without cryopreservation (24 cases) and with cryopreservation (9 cases); patients were diagnosed with AML in CR1 (n=21), ALL in CR1 (n=6), CML in CP (n=5) and non-Hodgkin's lymphoma in CR1 (n=1). The median age of the patients was 35 years (range 18-46). The median time to recover ANC >0.5 x 10(9)/l and platelet count >20 x 10(9)/l was 14 days (range 9-25 days) and 35 days (range 9-120 days). Following transplantation, 18 patients (54.50%) relapsed, 15 (45.45%) remained alive and overall survival times: 5.74+/-0.82 years and disease-free survival times: 5.48+/-0.92 years. There was no statistically significant difference of overall survival and disease-free survival between Allo-SCT and Auto-SCT procedures (P>0.05). These preliminary data suggest that HSCTs have been used as one of the standard treatments for hematological diseases and malignancies in Vietnam and that cord blood is an alternative source of hematopoietic stem cells for allogeneic transplantation in children.
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PMID:Current status of hematopoietic stem cell transplantations in Vietnam. 1872 91


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