High Number of Copy Number Alterations and Over-Expression of Genes Involved in the Response Mechanisms to Genotoxic Stress Both Characterize Newly Diagnosed Multiple Myeloma (MM) Patients Carrying Amplified MDM4 and/or Deleted p53,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3935-3935
Author(s):  
Carolina Terragna ◽  
Marina Martello ◽  
Sandra Durante ◽  
Lucia Pantani ◽  
Elena Zamagni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Copy Number ◽  
Plasma Cells ◽  
Genotoxic Stress ◽  
Newly Diagnosed ◽  
Copy Number Alterations ◽  
Over Expression ◽  
Expression Of Genes ◽  
Group A ◽  
Group B

Abstract Abstract 3935 Background The p53 tumor suppressor pathway is tightly kept in check, or completely silenced in cancer cells. A potent inhibitor of p53 is represented by MDM4, which is critical for the control of p53 activity during the response to stress and is often amplified in several types of cancer. TP53 mutations are rare in newly diagnosed MM, while occur more frequently as late event in the course of the disease and are related to survival. Recently, the adverse prognostic impact of chr. 1q amplification, described in almost 40% of newly diagnosed MM pts, has been reported. The minimal amplified region on chr. 1q harbors MDM4. Since both del(17p) and amp(1q) identify a subgroup of high-risk MM pts, even when the novel agents are part of up-front treatment strategy, we molecularly analyzed a subgroup of MM patients treated with bortezomib-thalidomide-dexamethasone (VTD) incorporated into autologous stem cell transplantation, in order to investigate mechanisms which might be activated in myeloma plasma cells to direct and/or indirect limit the p53 function. Methods Thirty eight pts treated with VTD incorporated into autologous stem cell transplantation were analysed by means of gene expression profile (Affymetrix U133 Plus2.0 array) and unpaired analysis of copy number alterations (CNA) (Affymetrix 6.0 SNP array). Both GEP and SNP arrays experiments were performed on highly purified CD138+ bone marrow plasma cells obtained at diagnosis from each pts. The presence of CNAs in chr.1 and 17 was evaluated to identify pts carrying amp(1q) and del(17p). Results Eighteen out of 38 pts (42%) carried a minimal amplification region of 1,1 Mb on chr.1q, which harbors MDM4. Five out of 38 pts (13%) carried a minimal deletion region of 482 Kb on chr.17, which harbors TP53. To explore the involvement of the p53 pathway in MM, pts were stratified according to the presence of amplified MDM4 and/or deleted p53 (group A, 18 pts) or the absence of both these abnormalities (group B, 20 pts). Baseline clinical characteristics were homogeneous, except for a higher rate of ≥ 3 bone lesions in pts carrying amplified MDM4 and/or deleted p53. The rate of best complete or near complete response was 89% in group A and 75% in group B. With a median follow-up of 36 months, the risk of relapse or progression was 50% for pts in group A and 25% for those in group B. The average number of aberrations per group was overall higher in group A as compared to group B (165 vs. 103 CNAs, p =0.03); indeed, the presence of amplified MDM4 and/or deleted p53 was significantly associated with a list of 95 CNAs (clustered on chr. 1, 2, 6, 8, 11, 13, 16 and 18), which included del16q (with a minimal area of deletion including WWOX), observed in 39% vs. 5% cases from group A and B, respectively (p<0.05) and chr.8 aberrations (with amplifications and or deletions, both including TRPS1) observed in 61% vs. 15% cases from group A and B, respectively (p<0.05). A comparison of expression profiles of patients carrying or not amplified MDM4 and/or deleted p53 confirmed the over-expression of MDM4 in the former group of pts and highlighted in these pts an overall activation of genes involved in the response mechanisms to genotoxic stress: indeed a significant over-expression of damage sensor genes (ATM, RAD9, RAD 50, ATRip), of damage signal mediator genes (H2AFX, 14-3-3), of genes involved in regulation of cell proliferation (CDK6, CDC25, CCND2) and of anti-apoptotic genes (BCL2, p73) was observed in pts with amplified MDM4 and/or deleted p53 (one-way ANOVA plus multiple-test correction with FDR <0,05). Finally, this group of pts significantly over-express the transcription factor YY1, which is known to interact with p53, thus inhibiting its transcriptional activity. Conclusions Pts carrying amplified MDM4 and/or deleted p53 showed a significantly higher number of CNAs and the significant over-expression of genes involved in the response mechanisms to genotoxic stress, as compared to pts lacking these chromosomal aberrations. This might account for the worse outcome of patients harboring del(17p) and/or amp(1q). The amplification of MDM4 locus and the over-expression of YY1 might contribute to maintain p53 in an OFF state by an indirect mechanism. Additional data on the role of both direct and indirect control of p53 pathway on VTD-treated MM pts prognosis, extended to an higher number of pts, will be presented during the meeting. Supported by: Fondazione Del Monte di Bo e Ra, Ateneo RFO grants (M.C.) BolognAIL. Disclosures: Cavo: Genzyme: Honoraria.

scholarly journals Melphalan Based Regimens for Treatment of Newly Diagnosed Amyloidosis, Lessons from Clinical Literature: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5561-5561
Author(s):  
Muhaddis Ejaz Ahmad ◽  
Muhammad Abdullah Yousaf ◽  
Abdul Rafae ◽  
Mustafa Nadeem Malik ◽  
Tariq Iqtidar Sadiq Syed ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cochrane Library ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Group A ◽  
Group B ◽  
High Dose Melphalan ◽  
Combination Regimens

Introduction: Melphalan causes cross linkage between DNA, causes cytotoxicity in both dividing and non-dividing tumor cells. Our objective is to analyze and summarize the published literature for the efficacy of melphalan based regimen used for the treatment of newly diagnosed Amyloidosis (ND-AL). Methods: We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after June 2006, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library and Web of Science. Total 649 articles were identified initially and after detailed screening, we finalized 10 studies involving 616 ND-AL patients. Results: Melphalan (M), Bortezomib (V) and dexamethasone (d)/prednisone (p): A retrospective study by Zhao et al., included 123 ND-AL patients (pts) were given M, V, and d. Overall hematological response (OHR) was 100% with complete response (CR) in 44% and partial response (PR) in 38.9% pts. Median overall survival (mOS) was 38 months (mo) and 3-yr survival ranged from 41-72%. Organ response (OR) was 25%. In a study by Lee et al., with 19 pts who received M, V, and p demonstrated OHR of 84% (Table 1). Melphalan (M) and dexamethasone (d): Sanchorawala et al. (n=70) reported patients treated with M and d showed OHR of 69%, with CR in 13% and PR in 25%. Similarly, a study by Lebovic et al. reported 40 pts who were given M, d. OHR was 58% and 13% pts showed CR (Table 1). High dose Melphalan/Stem Cell Transplant (HDM/SCT) with and without induction: In study by Cowan et al., (n=45) pts in group A (n=21) were given novel induction using agents like protease inhibitor (PI), cyclophosphamide, bortezomib and dexamethasone (CyBorD), Lenalidomide (L), dexamethasone (d) prior to high-dose melphalan (HDM). CR was observed in 50%, VGPR in 7% and PR in 7% pts. Group B (n=24) pts were given frontline HDM/SCT upfront. CR was observed in 28%, VGPR in 14% and PR in 14% pts. In a study by Scott et. al., 31 pts were categorized in 3 groups who received HDCT either with no induction, induction with V-based regimen and induction with other regimens including lenalidomide/dexamethasone (len/dex), melphalan/dexamethasone (mel/dex) and thalidomide/dexamethasone (Thal/dex). OHR in mel/dex cohort (n=3) was 67% (Table 1). In a study by Huang, X. et al., 56 pts were divided in two groups of 28 pts each. Pts in group A received Vd+HDM/SCT demonstrated CR in 67.9%, VGPR in 7.1%, PR in 10 .7 % and no response (NR) in 7.1 % pts. In group B, pts received with HDM/SCT upfront demonstrated CR in 35.7%, VGPR in 10.7%, PR in 2.1 % and no response NR in 21.4 % pts (Table 1). Randomized Standard dose Melphalan (SDM) versus HDM: In a study by Jaccard et al., there were two groups. The OHR was 68% in group A pts who were given SDM and high-dose dexamethasone (HD-dex) with CR in 31% and PR in 36% pts. The OHR was 67% in group B pts who were given HDM+ASCT with CR in 40% and PR in 25% pts (Table 1). Melphalan with Total body irradiaton (TBI): Vesole et al., reported 107 pts who were given M and TBI. OHR was 32% with CR in 16% and PR in 16% pts. mOS was 47.2 mo (Table 1). Melphalan (M), dexamethasone (d), Lenalidomide (L): In a clinical trial (NCT00890552) involving 25 pts M, d, and lenalidomide were give. CR, VGPR and PR were observed in 8%, 16% and 33%. 37.5% pts showed no-response (Table 1). Conclusion: Despite heterogeneity in the AL patient population and various regimens used in published literature, melphalan based regimens are very effective for treatment. Induction regimens and supportive care have evolved over the years. Novel combination regimens used for induction followed by HD-Melphalan consolidation along with careful selection of patients for high dose chemotherapy consolidation and stem cell transplantation in routine clinical practice is the best approach for personalized therapy selection for AL amyloidosis. Cytopenias of three cell lines are the major side effects reported with Mel therapy. Just like melphalan use for treatment of multiple myeloma in novel combination regimens, future randomized prospective trials are needed to better understand the efficacy and safety profile of melphalan based newer combination regimens for AL amyloidosis treatment. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease

2021 ◽  
Author(s):  
U. Thiel ◽  
S. J. Schober ◽  
A. Ranft ◽  
H. Gassmann ◽  
S. Jabar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Ewing Sarcoma ◽  
Chronic Gvhd ◽  
Risk Stratum ◽  
Group A ◽  
Status Number ◽  
Group B

AbstractPatients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus.

1987 ◽  
Vol 5 (8) ◽  
pp. 1143-1149 ◽  
Author(s):  
A A Forastiere ◽  
M Gennis ◽  
M B Orringer ◽  
F P Agha
Keyword(s):  
Pilot Trial ◽  
Transhiatal Esophagectomy ◽  
Newly Diagnosed ◽  
Surgical Specimen ◽  
Carcinoma Of The Esophagus ◽  
Group A ◽  
Tumor Measurements ◽  
Regional Disease ◽  
Group B

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).

Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients

Blood ◽  
2010 ◽  
Vol 116 (14) ◽  
pp. 2543-2553 ◽  
Author(s):  
Annemiek Broyl ◽  
Dirk Hose ◽  
Henk Lokhorst ◽  
Yvonne de Knegt ◽  
Justine Peeters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Plasma Cells ◽  
Medical Science ◽  
Protein Tyrosine Phosphatases ◽  
Molecular Classification ◽  
Newly Diagnosed ◽  
Expression Of Genes

Abstract To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities.

scholarly journals Mutation analysis and copy number alterations of KIF23 in non-small-cell lung cancer exhibiting KIF23 over-expression

2017 ◽  
Vol Volume 10 ◽  
pp. 4969-4979 ◽  
Author(s):  
Ann-Louise Vikberg ◽  
Tõnu Vooder ◽  
Kaie Lokk ◽  
Tarmo Annilo ◽  
Irina Golovleva
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mutation Analysis ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Small Cell ◽  
Copy Number Alterations ◽  
Small Cell Lung ◽  
Over Expression

Birth Order and Outcome in HLA-Identical Sibling Donor Hematopoietic Stem Cell Transplants. Impact of a Sequential Fetomaternal - Maternofetal Cell Transfer?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2034-2034
Author(s):  
Christoph M. Bucher ◽  
Dominik Heim ◽  
Andreas Buser ◽  
Jakob R. Passweg ◽  
Alois Gratwohl
Keyword(s):  
Stem Cell ◽  
Birth Order ◽  
Myeloid Leukemia ◽  
Cell Transfer ◽  
Black Line ◽  
Cell Transplants ◽  
Group A ◽  
Grade Ii ◽  
Stem Cell Transplants ◽  
Group B

Abstract Fetomaternal and maternofetal cell transfer have been described. Their clinical relevance is unknown. We hypothesized that firstborn siblings could tolerize their siblings born thereafter through sequential fetomaternal-maternofetal cell transfer. Hence, stem cell transplants within a family from a firstborn sibling (group A) should result more graft-versus-host disease (GvHD) and worse overall survival than transplants to a firstborn donor (group B). Results of a retrospective single center cohort analysis of 321 HLA-identical sibling donor hemopoietic stem cell transplants showed a survival of 48.3% (+/−10.9%) at 10 years in the group with firstborn donors (group A, 110 patients) as compared to 63.2 (+/−10.6%) in the group with firstborn recipients (group B, 105 patients; p<0.02) and a RR of death after adjustment for other risk factors of 2.6 (CI 1.45–4.66; p<0.001) for the group with firstborn donors. These results support the concept of a clinically relevant tolerizing effect of birth order, possibly mediated by fetomaternal cell transfer in man. Patients characteristics and outcomes Birth Order Donor First Sibling Recipient First Sibling n 110 105 Donor Age median (range) 30.1 (4.9–68) 25.4 (0.4–59.1) p=0.005 Recipient Age median (range) 25.4(3.2–62.1) 30.8 (2.2–63.0) Number of Siblings 2 67 69 n.s. 3 26 22 >3 17 14 Diagnosis n.s. Acute myeloid leukemia n 33 26 Acute lymphoblastic leukemia n 24 24 Chronic myeloid leukemia n 23 23 Lymphoproliferative disorders n 14 13 Severe aplastic anemia n 11 12 Myelodysplastic syndromes n 5 7 Stem Cell Source n.s. Bone Marrow n 71 73 PBSCT n 39 32 Conditioning n.s. With totoal body irradiation n 18 22 Without total body irradiation n 92 83 Outcomes Survival at 10 yrs % 48.3 63.2 p<0.02 Relapse at 3 yrs. % 26 20 n.s. Acute GvHD p=0.017 < Grade II n 46 61 >= Grade II n 64 44 Chronic GvHD n.s. none n 28 30 n.a. n 29 17 Limited n 32 30 Extensive n 21 23 Figure 1: Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient. Figure 1:. Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.

The Role of Alemtuzumab Compared to Antitymocyte Globulin in Non-Myeloablative Stem Cell Transplantation; Especially for the Prevention of GVHD and Immune Recovery.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2739-2739
Author(s):  
In Hae Park ◽  
June-Won Cheong ◽  
Jee Young Lee ◽  
Jin Seok Kim ◽  
Hyun Ju Chun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nk Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Immune Recovery ◽  
Cell Recovery ◽  
Myeloablative Conditioning ◽  
Gvhd Prophylaxis ◽  
Group A ◽  
Group B

Abstract Alemtuzumab is an anti-CD52 antibody, and has been used for lymphoid malignancies or as a member of non-myeloablative conditioning regimen in allogeneic transplantation. Especially, in non-myeloablative stem cell transplantation (NST), it has been reported that alemtuzumab is effective for graft-versus-host disease (GVHD), but the immune reconstruction after transplantation is delayed. In this study, we comparatively evaluated the efficacy of alemtuzumab for non-myeloablative conditioning, GVHD prophylaxis, and immune recovery in NST for hematologic diseases. We have compared the results in 28 recipients of a sibling or unrelated NST enrolled. The recipients were divided into 2 groups according to the use of alemtuzumab. In group A (n=21), the conditioning regimen was a combination of fludarabine, cyclophosphamide (or busulfan) and antithymocyte globulin (ATG), and group B (n=7) received fludarabine, cyclophosphamide (or busulfan), and alemtuzumab instead of ATG. GVHD prophylaxis was by cyclosporin A or FK506 plus methotrexate. There were no significant differences in the graft engraftment and period of granulocyte colony-stimulating factor infusion. Patients receiving alemtuzumab had a significantly lower incidence of acute GVHD (stage 2 or more) (14.3% versus 38.1%, P=0.03) and chronic GVHD (14.3% versus 52.4%, P=0.005). The relapse rate after transplantation was 28.6% (6 patients) in group A and 14.3 (1 patients) in group B (P=0.04). Flow cytometric analysis of peripheral mononuclear cells for evaluation of immune recovery showed that T-cell and NK-cell recovery were delayed in both groups. However, T-cell and NK-cell recovery after transplantation occurred earlier in patients received alemtuzumab. No significant differences were observed in disease-free or overall survival between two groups. In conclusion, alemtuzumab can be recommended for immune suppression in NST, with successful control over acute/chronic GVHD and inducing relatively earlier immune recovery after transplantation.

Subclinical Alterations in Coagulation in Patients during Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5292-5292
Author(s):  
Qian Jiang ◽  
Xiao Jun Huang ◽  
Kaiyan Liu ◽  
Huan Chen ◽  
Yuhong Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
Group A ◽  
Group B ◽  
D Dimer

Abstract Objective To evaluate the alterations in coagulation in patients during modified busulfan plus cyclophosphamide (BUCY) ± antithymocyte globulin (ATG) before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to assess the effect of ATG on coagulation system as part of conditioning regimen. Methods Thirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Nineteen patients from HLA-identical siblings (group A) were conditioned with modified BUCY regimen, included cytarabine (2g/m2 i.v., day -9), busulfan (4mg/kg p.o. in divided doses daily, day -8 to day -6), cyclophosphamide (1.8g/m2 i.v., day -5 and day -4) and Me-CCNU (250mg/ m2 p.o., day -3). Sixteen patients from HLA-mismatched family members or HLA-matched unreleated donors (group B) were conditioned with modified BUCY + ATG regimen, added cytarabine (4g/m2 i.v., day -10 and -9) and rabbit ATG (2.5mg/kg i.v., day -5 to day -2, SangStat S.A.S., France). Blood samples were obtained before the start of regimen until day +1 after allo-HSCT. The following laboratory parameters were measured: prothrombin time (PT), active partial thromboplastin time (APTT), Fgrinogen (Fg), antithrombin (AT), D-Dimer, Fgrin degradation product (FDP), platelet (PLT), liver enzymes and bilirubin. VIII:C, IX:C, XI:C and XII:C in some blood samples with prolonged APTT were determined. Clinical hemorrhagic symptoms were monitored. Results From day -5 of conditioning regimens, temporary lengthening of APTT, which peaked on day -3, occurred in 16/19 (84.2%) patients in group A and 19/19 (100%) patients in group B, continued rise in Fg occurred in 17/19 (89.5%) patients in group A and 19/19 (100%) patients in group B, a progressive decrease of PLT was observed in all patients of two groups. Alterations of Fg and PLT were more significant in group B compared to those in group A. Transient D-Dimer increase was detected only in group B on day -3. Among intrinsic pathway coagulation factors, XII:C and XI:C were decreased commonly and significantly when APTT was prolonged. No difference between the two groups could be found with regard to PT, FDP, AT and liver parameters which remained nearly in normal ranges. Most of patients in two groups did not have overt bleeding manifestations. Conclusions Modified BUCY ± ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen contained ATG has more significant effect on coagulation parameters.

Study on Gene Exppression Profiling Associated with Prognosis in AML (M2a).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4360-4360
Author(s):  
Fan Yi Meng ◽  
Jiaming Tang ◽  
Wenli Ma
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Oligonucleotide Microarrays ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Group A ◽  
Group B ◽  
Refractory Aml

Abstract Objective: to explore genes related to the prognosis of AML (M2a). Methods: 6 newly diagnosed AML were involved in this experiment and were divided into 2 groups. Group A: 3 AML (M2a) patients with continuous complete remission (CCR1) less than 6 months; Group B: 3 AML (M2a) patients with CCR1 more than 12 months. Bone marrow mononuclear cells were separated and mRNA was purified and labeled with Cy3 and Cy5 respectively, which were used to hybridize against the Agilent human 1B 60mer oligonucleotide microarrays. Results: in the 20173 genes tested, 22 genes were found to be expressed differently between these two groups, among them 10 genes were up-regulated in group A, and 12 genes were up-regulated in group B. Conclusion: with microarray assay, 22 genes including APP were found to be differently expressed in AML (M2a) treated with standard chemotherapy. These genes may be early indicators for the diagnosis as well as prognosis of the refractory AML.

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