Immune Reconstitution Impact on Overall Survival after Hematopoietic Haploidentical Stem Cell Transplantation

Abstract Introduction: Early immune reconstitution (EIR) is clinically relevant for the outcome of allogeneic hematopoietic stem cell transplantation. In the setting of unmanipulated haploidentical transplantation (Haplo-HSCT), some groups have identified the absolute leukocyte count on day +30 (ALC30) as an independent prognostic factor in terms of overall survival (OS), disease free survival (DFS) and infectious mortality (IM). The aim of this study was to evaluate the impact of EIR on OS, DFS and IM among patients who underwent Haplo-HSCT with postransplant cyclophosphamide (PTCy) at our institution. Patients and methods: Sixty-six patients received a Haplo-HSCT at our institution from July 2011 to February 2016. Conditioning regimen consisted of fludarabine, cyclophosphamide and busulfan. Forty-five percent of the patients received a myeloablative regimen, including busulfan for 3 or 4 days, while 55% were conditioned using a reduced intensity regimen with 1 or 2 days of busulfan. Graft-versus-host disease (GVHD) prophylaxis was based on PTCy, cyclosporine and mycophenolate mofetil. EIR was assessed by means of ALC30 (cellular analyzer DXH, Beckman Coulter®), CD3+ lymphocyte count on day +30 (CD3-30) and NK-lymphocyte count on day +30 (NK30), both determined by multiparametric flow cytometry (FC500 and Navios, Beckman Coulter®). The Kaplan-Meier method was used to evaluate OS rate and DFS rate. Differences in survival rate were assessed using the log-rank test. P values <0.05 were considered statistically significant. Results: We analyzed 66 patients, with a median follow-up of 17 months (8-31). The median age of the patients was 43 years (range 30-57), 77% were men. The diagnosis were: acute myeloid leukemia 33%, acute lymphoid leukemia 8%, chronic myeloid leukemia 6%, Hodgkin lymphoma 21%, non-Hodgkin lymphoma 17%, myelodysplastic syndrome 8%, myelofibrosis (MF) 4%, others 3%. Most patients were in complete remission at the time of the transplant (56%), while 21% were in partial remission and 23% with overt disease. CMV reactivation was documented in 74% of the patients, 8% developed a proven invasive fungal infection and 36% suffered from hemorrhagic cystitis. Median OS and DFS were 17 (8-31) and 13 months (7-26), respectively. IM rate was 27% at the end of follow up. ROC curves were used to determine the optimal cut-off values for each of the studied variables: 300 cells/µL for ALC30, 120 cells/µL for CD3-30 and 40 cells/µL for NK30 were chosen. Those patients with an ALC30 ≥ 300/µL had longer OS (p=0.001) and DFS (p=0.005). Median OS and DFS were 25 months vs. not reached (NR) and 13 months vs. NR respectively. Patients with CD3-30 ≥120/µL had better OS (p=0.07, non-significant) and similar DFS than those with CD3-30 <120/µL. No differences were observed for the NK30 in terms of OS and DFS. Cumulative incidence of IM was significantly lower in patients with an ALC30≥300 (p=0.001). Cumulative incidence of relapse was not affected by ALC30. Patients with CD3-30>120/µL had a lower incidence of relapse than patients with CD3-30<120/µL (p=0.06, non-significant). Conclusions: Our study supports the independent prognostic significance of early immune reconstitution after unmanipulated haploidentical transplantation with postransplant cyclophosphamide, previously described by other groups. Patients with an ALC30 count over 300 cells/µL have a statistically significant better overall survival, disease free survival and a lower cumulative incidence of infectious mortality. However, ALC30 seems to have no correlation with relapse rate. CD3+ and NK-cell total counts on day 30 seem to have less prognostic impact, according to our study. Disclosures No relevant conflicts of interest to declare.

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Autologous Bone Marrow Transplantation as an Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v110.11.5121.5121 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5121-5121

Author(s):

Andre S. Jung ◽

Asad Bashey ◽

Peter R. Holman ◽

Eva Carrier ◽

Januario Castro ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

Consolidation Therapy ◽

Free Survival ◽

Risk Patients ◽

Disease Free ◽

Acute Myeloid

Abstract Introduction: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myeloid leukemia. The optimal consolidation therapy for adults in remission without a histo-compatible donor has yet to be clearly established. Patients and Methods: This was a retrospective analysis of forty patients (23 females and 17 males) diagnosed with de novo acute myeloid leukemia, who were without a histo-compatible donor, that underwent APBSCT between the year 2000 and 2006 at a single institution. The patients’ age ranged from 18 to 73 with a median age of 50. Cytogenetic analysis was available on 37 of the patients. Complete remission (CR) was confirmed by bone marrow morphology and immunophenotype analysis by flow cytometry. Patients in remission were further consolidated with variable cycles of chemotherapy prior to stem cell transplantation. For stem cell mobilization, patients received high-dose cytarabine (2000mg/m2) and etoposide (5mg/kg) for three days followed by G-CSF at 10μg/kg, starting 10 days after the chemotherapy, before the peripheral stem cell collection. The preparative regimen prior to transplantation with unpurged stem/progenitor cells consisted of a combination of intravenous busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for two doses) (37 patients) or busulfan and melphalan (3 patients). Patients were then followed for treatment-related mortality, disease free survival, and overall survival. The analysis was stratified according to age, cytogenetic risk, and remission state. Results: There was no treatment-related mortality. Nineteen out of forty patients had relapse of their disease. The relapse rate was lowest in the low risk cytogenetic group who were under the age of 60 and highest in the high risk cytogenetic group who were over the age of 60. The overall 5 year survival for all patients was 47%. When stratified for cytogenetic risk and age, the overall survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 67%, 59%, and 75% respectively. The overall survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0% respectively. The projected rate of disease free survival at 5 years was 40%. When stratified for cytogenetic risk and age, the disease free survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 33%, 52%, and 50% respectively. Disease free survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0%. Comparing patients in CR1 versus patients in CR2, the overall survival was 47% in CR1 and 50% in CR2. The disease free survival, when grouped as above, were 41% for those in CR1 and 33% for those in CR2. Conclusion: APBSCT is a reasonable and safe intensive consolidation therapy for those patients without a compatible HLA matched donor in first or second complete remissions, notably for those under the age of 60 regardless of their cytogenetic risk. The number of standard consolidations prior to APBSCT may be an important variable predicting outcome.

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The Clinical and Biological Effects of the Expression of Dedicator of Cytokinesis 1 (DOCK1) in Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v128.22.1695.1695 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1695-1695 ◽

Cited By ~ 1

Author(s):

Lee Sze Hwei ◽

Wen-Chien Chou

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

Gene Set Enrichment Analysis ◽

Free Survival ◽

Disease Free ◽

Lower Expression ◽

Acute Myeloid

Abstract Background: DOCK1, also known as DOCK180, is the prototype member of the evolutionarily conserved DOCK superfamily. DOCK1 acts as a guanine nucleotide exchange factor (GEF) which regulates the activation of GTPase Rac, thereby influencing several cellular pathways including cell motility, polarity, invasion, phagocytosis and clearance of apoptotic cells. Overexpression of DOCK1 has been associated with cancer cell migration and invasion, however, its significance in acute myeloid leukemia (AML) remains unexplored. Materials and Methods: Expression patterns of DOCK1 were extracted from 347 AML patients recruited in the National Taiwan University Hospital (NTUH) (Illumina HumanHT-12 v4 Expression BeadChip, Illumina, San Diego, CA). We employed several public datasets, including microarray data of various lineages of normal hematopoiesis and AML marrow (GSE12662, GSE24006, and GSE24759) and The Cancer Genome Atlas (TCGA) RNA sequencing data of AML. In our cohort we analyzed the impacts of DOCK1 expression on various clinical parameters and genetic abnormalities. Survival was analyzed in 227 patients who received standard chemotherapy. The global gene expression profiles associated with DOCK1 expression was analyzed by bioinformatics tools. Two independent cohorts, TCGA (N=183) and GSE12417 (N=61), were used for validating the prognostic significance of DOCK1. Results: DOCK1 is a moderately expressed gene in AML (RPKM, 4.2; ranking, 50.5%). Higher DOCK1 expression level was associated with higher percentages of peripheral blasts (p=0.005), but inversely correlated with favorable cytogenetics such as t(8;21) and t(15;17). Moreover, mutations in CEBPA, c-KIT and IDH2 were less often seen in the patients with higher DOCK1 expression, while FLT3-ITD, and mutations in PTPN11, MLL, NPM1, RUNX1, ASXL1 and DNMT3A happened more often in those with higher DOCK1 expression. The Gene Set Enrichment Analysis (GSEA) of published stem cell signatures suggested DOCK1 as a hematopoietic and leukemic stem cell marker (GSEA P < 0.001 and = 0.004, respectively). Furthermore, it was generally co-expressed with homeobox genes, with average correlations ranging from 0.18 to 0.33 in normal samples, and 0.10 to 0.71 in AML datasets. With a median follow up of 57 months, we observed strong correlation between higher DOCK1 expression levels and inferior overall survival (OS) (median 18.0 months vs 116.8 months, P < 0.001) and disease free survival (DFS) (median 6.4 months vs 96.4 months, P < 0.001) (Figure 1A and 1B). These survival impacts could be validated in the two independent cohorts. In addition, multivariate analysis revealed higher DOCK1 expression as a strong unfavorable prognostic factor for OS (p=0.017) independent of age, karyotype, FLT3-ITD, and mutations of PTPN11, RUNX1, MLL and TP53. Conclusion: To our knowledge, we are the first to present the unique clinical, prognostic, and genetic impacts of DOCK1 in AML. Studies on large prospective cohorts are necessary to confirm our observation. The mechanistic functions of DOCK1 in AML await for further studies. Figure 1A Overall survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1A. Overall survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1B Disease free survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1B. Disease free survival of AML patients with higher expression versus lower expression of DOCK1 Disclosures No relevant conflicts of interest to declare.

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Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATCL): A Retrospective Study of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v118.21.3115.3115 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3115-3115

Author(s):

Esa Jantunen ◽

Ariane Boumendil ◽

Alessandro Rambaldi ◽

Marc Schapira ◽

Jian Jian Luan ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cell Lymphoma ◽

Disease Free Survival ◽

Free Survival ◽

History Of ◽

Disease Free

Abstract Abstract 3115 Background: EATCL is a rare subtype of peripheral T-cell lymphoma frequently observed in patients with a history of celiac disease. EATCL is characterized by poor prognosis when treated with conventional chemotherapy with only 10–20 % of long-term survivors. Limited data are available on feasibility and efficacy of stem cell transplantation in this lymphoma entity. Patients and methods: The database of the EBMT was used to identify patients with EATCL who had received autologous and/or allogeneic stem cell transplantation in 2000–2007. All centres reporting these patients were contacted to receive confirmation to histopathology report/pathology review and to obtain information in regard to treatment prior to stem cell transplantation and more recent follow-up data. Results: Altogether 85 patients with EATCL were identified. Seventy-three patients had received ASCT and 12 patients allogeneic SCT. Histological report/review with additional follow-up data was available from 22 ASCT treated patients which are reported here. There were 14 females (64 %) and eight males with a median age of 55 years at the time of transplant. Half of the patients had a history of coeliac disease. The median number of treatment lines before ASCT was 1 and 50 % of the patients were in the first remission at the time of ASCT. BEAM was the most commonly used high-dose regimen (17 pts, 77 %) and all patents received blood stem cell grafts. The median time from the diagnosis to ASCT was 6 months. The median follow-up time for living patients was 45 months from ASCT. During the follow-up relapse has been observed in 13 patients (59 %), the median time was only four months from ASCT. The median disease-free survival and overall survival were nine months and 15 months, respectively. Two-year overall survival, disease-free survival, cumulative incidence of relapse and non-relase mortality (NRM) was 45%, 40%, 55% and 4%, respectively. Conclusions: ASCT is feasible in selected patients with EATCL with a low NRM. Of transplanted patients 40 % remained disease-free beyond 2 years. This seems to be superior when compared to historical experiences although selection factors should be taken into account. ASCT is a treatment option in transplant eligible EATCL patients who respond to initial therapy. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia Transformed from Myelofibrosis

Blood ◽

10.1182/blood.v112.11.3293.3293 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3293-3293

Author(s):

Stefan O Ciurea ◽

Marcos De Lima ◽

Sergio Giralt ◽

Muzaffar H. Qazilbash ◽

Amin Alousi ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Acute Leukemia ◽

Allogeneic Stem Cell Transplantation ◽

Disease Free Survival ◽

Continuous Line ◽

Free Survival ◽

Disease Free

Abstract Background and Rationale: Transformation of myelofibrosis (MF) to acute leukemia (>20% blasts) portends a grave prognosis. Allogeneic stem cell transplantation (ASCT) is a curative approach for patients with acute leukemia; however, the outcomes of ASCT in patients with MF transformed to acute leukemia are currently unknown. Methods: Fifty-one consecutive patients with either primary (PMF) or secondary (SMF) were transplanted at UTMDACC after 1994. Thirteen patients who developed AML (25%), 10 arising from PMF and 3 with SMF, received an ASCT from a sibling or matched unrelated donor. Median age was 59 years. Five patients (38%) had prior splenectomy. JAK2V617F mutation analysis was performed in 7, and was present in 5 patients. Cytogenetics were intermediate in 10 and poor-risk in 3 patients. Seven patients (54%) were not in remission at the time of transplant. Eleven of 13 patients received induction chemotherapy; 6 achieved remission, while 7 had persistent disease at the time of transplant. One patient had a prior autologous transplant and 2 patients had prior allogeneic transplant for myelofibrosis. The donors were matched siblings (7 patients), matched unrelated (4 patients) and 1 antigen mismatched relatives (2 patients). The stem cell source was peripheral blood in 9 and bone marrow in 4 patients. Nine patients received a reduced-intensity conditioning regimen with a fludrabine-melphalan-based regimen, and 4 myeloablative conditioning (3 fludarabine-busulfan, 1 busulfan-cyclophosphamide). Results: All patients engrafted, 75% achieved full donor chimerism, on day 30. Neutrophil and platelet engraftment occurred after a median of 13 and 21.5 days. Twelve evaluable patients achieved remission; 3 subsequently relapsed. JAK2V617F mutation became negative after transplant in all tested patients and reappeared in 1 patient who later relapsed. Grade 2–4 aGVHD developed in 3 patients (grade 3–4 in one) and cGVHD in 4/11 evaluable patients (extensive in two). After a median follow-up of 17.2 months (range 7.2–128.6 mo), OS and EFS were 49% (SE 15%) and 44% (SE 14%), respectively (Figure1). Six patients died, related to disease relapse (2), pneumonia (2), GVHD (1), and hepatic failure (1). Conclusion: Patients with acute leukemia transformed from myelofibrosis with good performance status can achieve durable complete remissions with ASCT. Figure 1. Overall survival (continuous line) and disease-free survival (interrupted line) in 13 patients with acute leukemia transformed from MF post ASCT after a median follow-up of 17.2 months. Figure 1. Overall survival (continuous line) and disease-free survival (interrupted line) in 13 patients with acute leukemia transformed from MF post ASCT after a median follow-up of 17.2 months.

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Does microgranular variant morphology of acute promyelocytic leukemia independently predict a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group

Blood ◽

10.1182/blood-2010-06-288613 ◽

2010 ◽

Vol 116 (25) ◽

pp. 5650-5659 ◽

Cited By ~ 21

Author(s):

Martin S. Tallman ◽

Haesook T. Kim ◽

Pau Montesinos ◽

Frederick R. Appelbaum ◽

Javier de la Serna ◽

...

Keyword(s):

Overall Survival ◽

Retinoic Acid ◽

Cumulative Incidence ◽

Disease Free Survival ◽

Promyelocytic Leukemia ◽

Free Survival ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Disease Free

Abstract Few studies have examined the outcome of large numbers of patients with the microgranular variant (M3V) of acute promyelocytic leukemia (APL) in the all-trans retinoic acid era. Here, the outcome of 155 patients treated with all-trans retinoic acid–based therapy on 3 clinical trials, North American Intergroup protocol I0129 and Programa para el Estudio de la Terapéutica en Hemopatía Maligna protocols LPA96 and LPA99, are reported. The complete remission rate for all 155 patients was 82%, compared with 89% for 748 patients with classical M3 disease. The incidence of the APL differentiation syndrome was 26%, compared with 25% for classical M3 patients, and the early death rate was 13.6% compared with 8.4% for patients with classical M3 morphology. With a median follow-up time among survivors of 7.6 years (range 3.6-14.5), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse for patients with M3V were 70%, 73%, and 24%, respectively. With a median follow-up time among survivors of 7.6 years (range 0.6-14.3), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse among patients with classical M3 morphology were 80% (P = .006 compared with M3V), 81% (P = .07), and 15% (P = .005), respectively. When outcomes were adjusted for the white blood cell count or the relapse risk score, none of these outcomes were significantly different between patients with M3V and classical M3 APL.

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Two or More Chemotherapy Consolidation Courses, Followed By Autologous Bone Marrow Transplantation, and MRD Negativity, Give Long Term Overall Survival in Acute Myeloid Leukemia Patients

Blood ◽

10.1182/blood.v126.23.3198.3198 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3198-3198

Author(s):

Giovanni Marconi ◽

Cristina Papayannidis ◽

Federico Mosna ◽

Michele Gottardi ◽

Giorgia Simonetti ◽

...

Keyword(s):

Overall Survival ◽

Myeloid Leukemia ◽

Autologous Bone Marrow Transplantation ◽

Disease Free Survival ◽

Normal Karyotype ◽

Autologous Bone Marrow ◽

Free Survival ◽

Disease Free

Abstract Introduction. Autologous Bone Marrow Transplantation (Auto-BMT) is currently rarely used in the treatment of Acute Myeloid Leukemia (AML). However, it may represent a good therapeutic option in a specific subset of patients, mainly in consolidation of both low risk (LR) and MRD negative AML without an available HLA matched donor. Aims. To review our database of AML patients who received Auto-BMT from 2005 to 2014 and who were referred to Bologna Institution, in order to assess the efficacy of the procedure in terms of Overall Survival (OS) and Disease Free Survival (DFS). Patients and methods: From 2005 to 2014, 98 AML patients underwent Auto-BMT in several Italian Institutions. 89/98 patients are evaluable for survival and outcome data. The 89 patients considered (42 female, 47 male), had a median age of 49 years (range 15-70). Cytogenetics was performed in all patients by conventional karyotype (22 patients were also analyzed by Single Nucleotide Polymorphisms Array); molecular analysis (FLT3 TKD and ITD, and NPM1 mutational analysis) was available for 51/89 patients. Molecular monitoring by specific fusion transcripts (CBF-MYH11 and AML1-ETO) was performed in CBF positive leukemias (inv(16) and t(8;21)) at the time of diagnosis, after induction, consolidation courses, and every 3 months in the first 2 years of follow-up. Based on this data, and according to ELN guidelines, a risk stratification identified 41 patients with a LR AML (t(8:21), inv(16) or NPM1+/FLT3- with normal karyotype), 4 patients with a high risk (HR) AML (complex karyotype or FLT3 ITD mutated or inv(3) or t(6;9)) and 44 patients with a standard risk (SR) AML (normal karyotype, other alterations). Results. All the patients received an induction chemotherapy treatment, as follows: a "3+7-like" course in 48 cases, a Fludarabine-based regimen in 20 patients and a Gemtuzumab-ozogamicin (GO)-based regimen in 21. 83/89 (93.3%) patients received a median of 2 consolidation courses of chemotherapy (range 1-4) before proceeding to Auto-BMT, performed in 1st CR. 6/89 (6.7%) patients received Auto-BMT in first relapse. 41 patients relapsed after auto-BMT and were treated with a re-induction chemotherapy, or were enrolled in clinical trials. 24 patients reached a 2nd complete remission, and 12 patients underwent an allogeneic BMT in 2nd CR. With a median follow up of 6 years, the median Overall Survival (OS) of the entire population was 64.3 months (range 5.8-294.2 months); the 1 year OS and the 5 years OS were, 97.1%, and 67.9%, respectively. The median Disease Free Survival (DFS) of the 83 patients treated with Auto-BMT in 1st CR was 36 months (range 1.3-293 months). The 1-year DFS and the 5-years DFS were 85% and 56.7%, respectively. Transplant related mortality (TRM, death in 100 days after BMT) was 1.2% for auto-BMT and 6.5% for allogeneic BMT. First, to assess the role of the number of consolidation courses we compared patients who received none or 1 consolidation course with patients who received 2 or more cycles, who showed a better OS (p= 0.0061, Figure 1). There was no statistical difference in terms of OS between young and elderly patients (cut off=65 years). Second, we compared patients who achieved a negative minimal residual disease status before auto-BMT (n=37) with patients who did not (n=9). MRD negativity offered a significantly better outcome in terms of 5-years OS (83.4% and 50% respectively); the median OS of MRD neg was not yet reached; the median OS of MRD pos was 27 months (p= 0.0130) (Figure 2). Conclusions: Auto-BMT offers a chance to achieve long-term DFS and OS if used as a consolidation therapy both in patients with LR and SR AML. The major role could be played in MRD negative patients, offering the best chances to achieve a long-term OS. Auto-BMT can be also a good choice as consolidation therapy for elderly patients, in which allo-BMT could induce high morbidity and mortality rates. The small patients cohort and the retrospective analysis don't allow us to define the best induction therapy to be used before auto-BMT. However, based on our findings we suggest a therapy schedule including two or more consolidation courses in patients who obtain a first CR, and to proceed then to auto-BMT. Acknowledgments: work supported by ELN, AIL, AIRC, Progetto Regione-Università 2010-12 (L.Bolondi), Fondazione del Monte di Bologna e Ravenna, FP7 NGS-PTL project. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Soverini: Novartis, Briston-Myers Squibb, ARIAD: Consultancy. Rodeghiero:Celgene Corporation: Honoraria, Research Funding. Cavo:Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Martinelli:AMGEN: Consultancy; Novartis: Consultancy, Speakers Bureau; Ariad: Consultancy; BMS: Consultancy, Speakers Bureau; ROCHE: Consultancy; Pfizer: Consultancy; MSD: Consultancy.

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Clonal Gammopathies Following Reduced Intensity Conditioning Transplantation with Fludarabine, Busulphan and Alemtuzumab for Myeloid Malignancies Predict Improved Overall Survival.

Blood ◽

10.1182/blood.v106.11.1410.1410 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1410-1410

Author(s):

ZiYi Lim ◽

Antonio Pagliuca ◽

Wendy Ingram ◽

Dragana Milojkovic ◽

Mojtaba Akthari ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Disease Free Survival ◽

Autoimmune Disorders ◽

Disease Stage ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Myeloid Malignancies ◽

Disease Free

Abstract Clonal gammopathies and autoimmune disease following standard conditioning haematopoietic stem cell transplantation (HSCT) are thought to reflect immune dysregulation post HSCT. Serial serum protein electrophoresis was performed on 124 patients with myeloid malignancies undergoing Alemtuzumab based reduced intensity conditioning (RIC) HSCT. The median age of patients was 53 years (range 22–72), with a median follow-up of 521 days (range 82–2096). The median follow-up for survivors was 720 days (range 82–2096). The majority of patients were treated for myeloid malignancies: MDS 84, AML 28, CML 10, others 2. There were 45 sibling and 79 VUD allografts. All patients received the same RIC protocol with FBC (30mg/m2 fludarabine iv day −9 to −5, 4 mg/kg busulphan oral from day −3 to −2; and 20 mg alemtuzumab iv from day −8 to −4) conditioning with cycloporine A for GvHD prophylaxis. Patients with autoimmune disorders or clonal gammopathies prior to transplant were excluded from the study. We observed the presence of clonal gammopathies in 49 patients (40%). On analysis of immunoglobulin sub-classes, the M component was identified as monoclonal in 21 (43%), biclonal in 16 (33%) and oligoclonal in 12 (24%). The predominant Ig isotype was IgG (84%), and gammopathies were present for a median time of 138.5 days (range: 27–462). The kappa:lambda ratio between samples was 1.6:1. The median level of gammopathies was 2.6 g/l (range 1.0–16.5). There was no evidence of plasma cell dyscrasia on bone marrow assessment in any of the patients. We compared the characteristics of patients with and without gammopathies. There were no significant differences in donor or recipient age, sex, disease type, stem cell source, stem cell dose. The incidence of viral infections, acute GvHD, donor lymphocyte infusion (DLI) was similar between the groups. However, patients with gammopathies were more likely to have chronic graft versus host disease (GvHD) (p=0.006). Bone marrow chimerism was available for analysis on 45 patients. At time of detection of gammopathy, 34 patients (76%) had achieved full donor chimerism, and 11 patients (24%) were mixed donor chimerism. Of the entire group of 124 patients, 11 patients (9%) developed autoimmune disorders. There was however no association between the presence of autoimmune disorders and clonal gammopathies (p=0.50). When patients with gammopathies were compared with those without, there was a significant difference in both disease free survival (54% vs 24%, p=0.012), and overall survival (69% vs 45%, p=0.007). On univariate analysis, early disease stage and presence of gammopathy were significant predictive variables for improved disease free survival and overall survival. On multivariate analysis, disease stage was the only independent variable for disease free survival (p<0.01, HR 2.345, 95% CI 1.282–4.288), and both disease stage (p=0.05, HR 1.901, 95% CI 1.000–3.615) and presence of gammopathy (p=0.01, HR 0.421, 95% CI 0.217–0.815) were independent predictors of overall survival. The role of humoral responses following transplantation is still undefined, and it is possible that the gammopathies seen in our cohort are a surrogate response to a heterogenous group of stimuli. Clonal gammopathies are a frequent and benign occurrence following RIC HSCT, and its appearance may define a subgroup of patients with a favourable overall outcome.

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Predictable Prognostic Factor of CD56 Expression in Acute Myeloid Leukemia with t(8:21) Including Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v106.11.3288.3288 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3288-3288

Author(s):

Deok-Hwan Yang ◽

Yeung-Chul Mun ◽

Ho-Jin Shin ◽

Yeo-Kyeoung Kim ◽

Je-Jung Lee ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Disease Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Cd56 Expression ◽

Disease Free ◽

Acute Myeloid

Abstract CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multi-drug resistance, but the clinical and prognostic significances are not yet clearly defined. Recently, some investigators reported that AML patients with t(8;21) showed more frequent CD56 expression rate and the expression of CD56 antigen adversely affected disease-free survival (DFS). It could explain a diverse clinical outcome in AML patients with favorable cytogenetics. This study investigated CD56 expression in 37 adult de novo AML patients with t(8:21) between November 1996 and June 2005 at three institutions. Immunophenotyping was performed with flow cytometry (Coulter EPICS XL) and considered positive if at least 20% of blasts expressed. CD56 was expressed in 25 cases (67.6%). There was no statistically significant differences in age, sex, leukocyte count, the percentage of bone marrow blasts or the presence of additional cytogenetic abnormalities between the CD56+ and the CD56- group. The complete remission (CR) rate to standard dose cytarabine or N4-behenoyl-1-D-arabinofuranosylcytosine (BH-AC) and idarubicin was similar in both groups (91.7% v 88.7%; P=0.73), but the relapse rate to high-dose cytarabine or allogeneic hematopoietic stem cell transplantation (HST) was quite different (60% v 25%; P=0.08). Allogeneic HST was performed from siblings in 15 patients (40.5%) who achieved CR, 8 patients (32.0%) in CD56+ and 7 patients (58.3%) in CD56- group (P=0.16). The median durations of DFS were significantly shorter in CD56+ (median, 12.2 months) than in the CD56- group (median, not reached) (P =0.02). Also, the median durations of survival showed the same results in the CD56+ group (median, 14.9 months) compared with the CD56- group (median, not reached) (P=0.01). Within fifteen transplanted patients, the median durations of DFS in eight CD56+ patients was significantly shorter than seven CD56- patients (median, 24.4 months v not reached; P=0.02)(Fig.1 and 2).We concluded that CD56 expression was associated with reduced DFS and survival for AML patients with t(8:21) including transplanted patients. Although further larger studies are needed, we suggested that CD56 expression at diagnosis is a predictable prognostic factor in AML with t(8:21). Fig. 1 Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 1. Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 2 Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression. Fig. 2. Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression.

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Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002587 ◽

2021 ◽

pp. ijgc-2021-002587

Author(s):

Felix Boria ◽

Luis Chiva ◽

Vanna Zanagnolo ◽

Denis Querleu ◽

Nerea Martin-Calvo ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Quality Indicators ◽

Radical Hysterectomy ◽

Disease Free Survival ◽

Free Survival ◽

Operative Complications ◽

Early Cervical Cancer ◽

Disease Free

IntroductionComprehensive updated information on cervical cancer surgical treatment in Europe is scarce.ObjectiveTo evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database.MethodsThe SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified.ResultsThe mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0–84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation.ConclusionsIn this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

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Ecoendoscopia en la estadificación del cáncer de esófago y de estómago

Revista Argentina de Cirugía ◽

10.25132/raac.v113.n1.1524.ei ◽

2021 ◽

Vol 113 (1) ◽

pp. 32-42

Author(s):

Martín Galvarini Recabarren ◽

◽

Francisco Schlottmann ◽

C. Agustín Angeramo ◽

Javier Kerman Cabo ◽

...

Keyword(s):

Overall Survival ◽

Neoadjuvant Therapy ◽

Preoperative Staging ◽

Disease Free Survival ◽

Perioperative Chemotherapy ◽

Free Survival ◽

Causes Of Mortality ◽

Node Metastases ◽

Disease Free

Background: Gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) are one of the leading causes of mortality from gastrointestinal cancer worldwide. Endoscopic ultrasound (EUS) has proved to be a valuable tool for preoperative staging of GAC and EAC in selected cases. Objective: The aim of this study was to evaluate the usefulness of EUS for staging of EAC and GAC and selecting patients who are candidates for neoadjuvant therapy, as compared with the previous stage before the implementation of EUS, in a surgical center in Argentina. Material and methods: Consecutive patients with EAC and GAC between 2013-2019 were included. Patients with criteria of unresectable cancer or who underwent emergency surgery were excluded. The sample was divided into four groups G1 and G2 (EAC with and without EUS, respectively) and G3 and G4 (GAC with and without EUS, respectively). The clinical and anatomopathological variables and survival were evaluated in all the groups. Results: A total of 89 patients were included, 40 with EAC (30 in G1 and 10 in G2, and 49 with GAC, 20 in G3 and 29 in G4. Of the patients undergoing EUS staging in G1, 23 (75%) received neoadjuvant therapy vs. 2 patients in G2 (20%) (P ≤ 0.005). Eight patients (40%) in G3 and 2 (7%) in G4 received perioperative chemotherapy (P ≤ 0.005). Lymph node metastases were observed in 9 (30%) of surgical specimens of EAC in G1 and in 60% in G2 (P ≤ 0.005), and in 45% in G3 and G4. After a mean follow-up of 36 months (6-72), we observed a non-significant trend toward higher overall survival and disease-free survival in patients undergoing EUS staging. Conclusion: EUS for preoperative staging pf EAC and GAC is a useful tool. Although the use of EUS use may be a challenging task in many centers in Argentina, future efforts are needed to include this test in selected cases for staging patients with these types of cancers

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