scholarly journals Association between HLA-D region antigens and disease-free survival in childhood non-T, non-B acute lymphocytic leukemia

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 698-702
Author(s):  
JT Casper ◽  
M Marrari ◽  
V Piaskowski ◽  
SJ Lauer ◽  
RJ Duquesnoy
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Genetic Factors ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Hla Dr ◽  
D Region ◽  
Table Analysis ◽  
Disease Free ◽  
Normal Controls

The frequency of three serologically defined HLA-D region antigens--DR, MB, and MT--was determined in a group of 74 children with non-T, non-B acute lymphocytic leukemia (ALL). Statistically, there were no significant differences in the frequency of any antigen in these ALL patients as compared with a panel of 85 normal controls. However, significant differences in HLA-DR frequencies were observed between patients who relapsed or who remained disease-free during a 30-mo period of chemotherapy. An increased incidence of relapse was associated with DR5, while disease-free remission during chemotherapy was associated with DR7. Life table analysis also demonstrated that DR5 was significantly associated with a decrease in disease-free survival in these patients. These data suggest that HLA-associated genetic factors may influence the responses of ALL patients to chemotherapy.

scholarly journals Association between HLA-D region antigens and disease-free survival in childhood non-T, non-B acute lymphocytic leukemia

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 698-702 ◽  
Author(s):  
JT Casper ◽  
M Marrari ◽  
V Piaskowski ◽  
SJ Lauer ◽  
RJ Duquesnoy
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Genetic Factors ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Hla Dr ◽  
D Region ◽  
Table Analysis ◽  
Disease Free ◽  
Normal Controls

Abstract The frequency of three serologically defined HLA-D region antigens--DR, MB, and MT--was determined in a group of 74 children with non-T, non-B acute lymphocytic leukemia (ALL). Statistically, there were no significant differences in the frequency of any antigen in these ALL patients as compared with a panel of 85 normal controls. However, significant differences in HLA-DR frequencies were observed between patients who relapsed or who remained disease-free during a 30-mo period of chemotherapy. An increased incidence of relapse was associated with DR5, while disease-free remission during chemotherapy was associated with DR7. Life table analysis also demonstrated that DR5 was significantly associated with a decrease in disease-free survival in these patients. These data suggest that HLA-associated genetic factors may influence the responses of ALL patients to chemotherapy.

Second or Subsequent Remission With a Disease-Free Survival of 5 Years or Longer in Acute Lymphocytic Leukemia of Childhood: Results of a National Survey

PEDIATRICS ◽  
1986 ◽  
Vol 77 (5) ◽  
pp. 765-769
Author(s):  
Stanley Musgrave ◽  
Joseph D. Dickerman ◽  
Vita J. Land
Keyword(s):  
National Survey ◽  
Acute Lymphocytic Leukemia ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Number Of Children ◽  
Disease Free

A national survey was conducted to determine the number of children with acute lymphocytic leukemia who have survived 5 years or longer in their second or subsequent remission. Seventy-two such patients were identified. The clinical and laboratory characteristics of these patients as well as their therapy are described. It is concluded that long-term second or subsequent remission may occur more frequently than previously appreciated.

De-Intensification of the Chemotherapy Did Not Affect the Outcome of Ph-Positive Acute Lymphocytic Leukemia Patients in the Era of Tyrosine Kinase Inhibitors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2805-2805
Author(s):  
Olga A. Gavrilina ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Andrey N. Sokolov ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Complete Remission ◽  
Acute Lymphocytic Leukemia ◽  
Kinase Inhibitors ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Disease Free

Abstract Introduction. For more than a decade it's postulated that the addition oftyrosine kinase inhibitors (TKI) to chemotherapy has dramatically improved the long term outcome in Ph-positive adult acute lymphoblastic leukemia (Ph+ ALL). Nevertheless whether do we need chemotherapy at all and if yes - how intensive it should be, is still the matter of debates. The only randomized trial addressing this issue (GRAAL, Blood 2015, 125: 3711-3719) has demonstrated the lack of benefit of more intensive induction at all checkpoints: complete remission (CR) rate, major molecular complete remission (MMolCR), molecular complete remission (MolCR), progression disease (PD) and resistance. We have conducted two consecutive trials in Ph+ ALL aiming to evaluate the efficacy of more and less intensive chemotherapy approach in combination with constant non-stop 600 mg Imatinib application. Aim. Toanalyze of the protocol RALL-2009 with ITK and RALL-Ph+-2012 effectiveness in patients with Ph+ ALL. The primary objective was the major molecular complete remission (MMolCR) rate after induction (70th day), patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. Patients and methods. Since Jan 2010 till July 2016, 120 new cases of ALL were verified in our National Research Center for Hematology with 68 (56,7%) of them being B-cell precursors ALL and 25 diagnosed as Ph-positive (36,8%). Since 2010 till 2012, 10 Ph+ ALL pts (median age 35 years (19-68), m/f (50%)/(50%), CNS disease=1, WBC> 30*109/l=5(50%), bcr/abl transcript p190/p210/p190+210 6(60%)/3(30%)/1(10%)) were treated according to RALL-2009 protocol (ClinicalTrials.gov public site; NCT01193933) with parallel Imatinib. This protocol includes 8 cytostatic drugs and no intervals between treatment phases. Since 2012 till now 15 other pts (median age 40 years (17-61); m/f 7(46,7%)/8(53,3%); CNS disease=1, WBC>30*109/l=5(33,3%), bcr/abl transcript p190/p210/p190+210 9(60%)/5(33%)/1(7%)) were included in RALL- Ph+-2012 protocol, based mainly on 600 mg Imatinib with prednisolone, VNCR, L-asp, followed by 6-MP and MTX. Both protocols suggested the shift to Dasatinib (100-140 mg) after non-achievement of MolCR at day 70 of treatment. MolCR was stated if no bcr/abl chimeric transcript was detected by PCR with 10-4 sensitivity. All patients were considered as candidates for allogeneic HSCT if HLA-identical donor was available. Results. At day 70th disregarding the chemotherapy intensity there was 40% of MolCR on both protocols (RALL-2009 - n=4 and RALL-2012 - n=6). No death within 2 months of induction/consolidation were registered on less intensive protocol in comparison with 2 cases on RALL-2009. Hematological CR was achieved in all pts (except two early deaths on RALL-2009) - 23 of 25 (92%). There was one autologous HSCT in older pts, included in RALL-2012 (n=3, aGVHD and severe infections, at a median +4 months after HSCT and more than 12 months of CR duration). The 3y OS, DFS and relapse probability (RP) for all 25 pts constituted 37,8%, 32,5% and 52,1% (Fig. 1). The long-term outcome on both protocols (RALL-2009 and RALL-2012) was similar: OS - 45% vs 27,7% (p=0,27), DFS - 45% vs 22,1% (p=0,94), RP - 35,7% vs 57% (p=0,29), respectively (Fig.2). Conclusion. De-intensification of the chemotherapy does not affect the effectiveness of the therapy Ph-positive acute lymphocytic leukemia in era of the tyrosine kinase inhibitors. We haven't seen differences in achievement of molecular remission when we deescalated chemotherapy (40% vs. 40%). However, when we reduced toxicity of the chemotherapy in ALL-2012 protocol, we were able to realize more extra allo-BMT and it could improve long-term results of the therapy Ph+ ALL. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL protocols. Figure Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Figure. Overall, disease-free survival and relapse probability in patients with Ph+ ALL on RALL-2009 and RALL-2012 protocols. Disclosures No relevant conflicts of interest to declare.

Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Donald W. Milligan ◽  
Savio Fernandes ◽  
Ranjit Dasgupta ◽  
Faith E. Davies ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Free Survival ◽  
Number Of Patients ◽  
Disease Free

Abstract We have assessed autologous stem cell transplantation after treatment with fludarabine in previously untreated patients with chronic lymphocytic leukemia (CLL). This study is the first to enroll previously untreated patients and follow them prospectively. The initial response rate to fludarabine was 82% (94 of 115 patients). Stem cell mobilization was attempted in 88 patients and was successful in 59 (67%). Overall 65 of 115 patients (56%) entered into the study proceeded to autologous transplantation. The early transplant-related mortality rate was 1.5% (1 of 65 patients). The number of patients in complete remission after transplantation increased from 37% (24 of 65) to 74% (48 of 65), and 26 of 41 patients (63%) who were not in complete remission at the time of their transplantation achieved a complete remission after transplantation. The 5-year overall and disease-free survival rates from transplantation were 77.5% (CI, 57.2%-97.8%) and 51.5% (CI, 33.2%-69.8%), respectively. None of the variables examined at study entry were found to be predictors of either overall or disease-free survival. Sixteen of 20 evaluable patients achieved a molecular remission on a polymerase chain reaction (PCR) for immunoglobulin heavy-chain gene rearrangements in the first 6 months following transplantation. Detectable molecular disease by PCR was highly predictive of disease recurrence. It is of concern that 5 of 65 (8%) patients developed posttransplant acute myeloid leukemia/myelodysplastic syndrome. (Blood. 2005;105:397-404)

Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy.

1989 ◽  
Vol 7 (1) ◽  
pp. 50-57 ◽  
Author(s):  
J Mortimer ◽  
M A Blinder ◽  
S Schulman ◽  
F R Appelbaum ◽  
C D Buckner ◽  
...  
Keyword(s):  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Early Death ◽  
Marrow Transplant ◽  
Lymphocytic Leukemia ◽  
Late Relapse ◽  
Free Survival ◽  
High Incidence ◽  
Low Probability ◽  
Disease Free

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.

Impact on Progression Free Survival of Autologous Stem Cell transplantation after Consolidation with Alemtuzumab in Chronic Lymphocytic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2182-2182
Author(s):  
Marco Montillo ◽  
Francesca Ricci ◽  
Alessandra Tedeschi ◽  
Sara Miqueleiz ◽  
Giovanni Grillo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Richter Syndrome ◽  
Cell Harvest ◽  
Cmv Reactivation ◽  
Disease Free

Abstract The role of an intensified program of autologous stem cell transplantation (ASCT) following a consolidation phase with alemtuzumab (A) in pts with chronic lymphocytic leukemia (B-CLL) who received a fludarabine-based regimen (Fbr) as debulking is still considered questionable. The reported evidence of a prolonged treatment free-survival and survival associated to the absence of minimal residual disease (MRD) in B-CLL pts treated with A doesn’t seem to justify an intensification with ASCT in case of MRD-. We have already reported our experience in B-CLL pts treated with Fbr who after a median period of discontinuation of 16 weeks, received A sc (10 mg x 3/w for six weeks) in order to obtain the maximum response of MRD negative remission. Pts obtaining a successful peripheral blood stem cell harvest (PBSC) were considered eligible for ASCT. After a longer follow-up period we analyze here the outcome of autografted pts. Furthermore results were compared with those of pts treated with the same regimen but excluded from transplant procedure. Overall 48 pts have been considered for the analysis. Twenty-nine pts underwent an ASCT. Mobilization regimen consisted in all but 1 pt of Ara-C (800 mg/ sqm/12h x 3 days) followed by granulocyte colony-stimulating factor (G-CSF) while the last patient received only G-CSF. Reason for exclusion from ASCT procedure in the 19 non transplanted pts was: 9 refusal, 4 progressive disease, 1 evolution to Richter syndrome, 2 priming failure, 3 physician decision. Initially, in the group of non-transplanted pts, 9 (47%) were in stage A, 9 (47%) B, 1 (6%) C; ZAP70 was positive in 4 (21%) cases. Response after consolidation with A was: 7 MRD- CR (37%), 7 MRD+ CR (37%), 1 PRn (5%), 4 PR (21%). As regards the transplanted pts: 9 (31%) were in stage Binet A, 16 (55%) B, 4 (14%) C; ZAP70 was positive in 10 (34%) cases. Disease status after A was as follows: 18 MRD- CR (62%), 6 MRD+ CR (21%), 5 PRn (17%). Median age at transplant was 55 years (range 44–64). In all pts a reassessment of response status was ruled out before transplant to exclude a disease progression. ASCT procedure was performed after a median of 12 mos from last A administration (range 6.5–16.8). One pt who reactivated a virus B hepatitis after consolidation was successfully transplanted after 16.8 mos interval from alemtuzumab. Conditioning regimen consisted of 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg in 21 pts <60 years, and melphalan 180 mg/m2 in 8 pts ≥60 years. Median number of CD34+ cells reinfused was 14x106/kg (range 3.1–41); in 15 cases (52%) the reinfused product was polyclonal for IgH rearrangement. The median time for PMN ≥500/mcL and PLT ≥20,000/mcL recovery was 9 (range 6–10 days) and 10 days (range 3–13 days) respectively. No incidence of grade 3–4 non hematologic toxicity was observed. None of the patients developed CMV reactivation, even in pts who showed a CMV reactivation during A treatment. One patient died (TRM 3.4%) due to a pulmonary fungal infection sustained by Aspergillus terreus. Disease assessment after transplant showed MRD- CR in 25 (86.2%) pts, in the remaining pts 2 MRD+ CR and 1 PRn were detected. In the transplanted population after a median follow-up of 46.3 mos (range 15.2–73.4) from last A administration and 35 mos from ASCT (range 2–59.8 months) 82% of pts are in CR according to NCI WG criteria. After the same follow-up period 20 (69%) pts are still in MRD- CR. Two pts died, one in MRD- CR for a lung cancer and one for fungal infection after transplant, two relapsed, after 45 and 15 mos respectively. In the non-transplanted pts after a median followup of 12 mos (range 1.5–64.2) from A 13 (68%) pts relapsed. Six pts died, 3 for disease progression, 1 for breast cancer, 1 for Richter syndrome and 1 for IMA while in MRD- CR. In conclusion in our experience ASCT following a chemo-immunotherapy confers a long disease free survival at 5 years (82%). Even if the population of non transplanted is not directly comparable, as transplanted pts were selected based on their response and the adequacy of the stem cell harvest, it is remarkable that in those pts the 5 year disease free survival is only of 32%. The in vivo “purging” effect of A given as consolidation facilitated the achievement of an high rate of MRD- PBSC collections. We can speculate that the reduced contamination of the reinfused product translated in sustained molecular remission after transplant. Moreover, this prospective single centre survey showed a low treatmentrelated mortality and absence of secondary MDS.

scholarly journals Biomarker roles identification of miR-106 family for predicting the risk and poor survival of colorectal cancer

2020 ◽  
Author(s):  
Qiliang Peng ◽  
Yi Shen ◽  
Peifeng Zhao ◽  
Ming Cheng ◽  
Yaqun Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanism ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Poor Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
Disease Free ◽  
Normal Controls

Abstract Background: Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.Methods: We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis. Results: The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23-2.44) and overall survival (HR: 1.39; 95%CI: 1.09-1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.Conclusions: Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.

Identification of the biomarker roles of miR-106 family for predicting the risk and poor survival of colorectal cancer

2019 ◽  
Author(s):  
Qiliang Peng ◽  
Yi Shen ◽  
Peifeng Zhao ◽  
Ming Cheng ◽  
Yaqun Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanism ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Poor Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis ◽  
Disease Free ◽  
Normal Controls

Abstract Background: Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.Methods: We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis. Results: The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23-2.44) and overall survival (HR: 1.39; 95%CI: 1.09-1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.Conclusions: Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.

scholarly journals Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia

Blood ◽  
2016 ◽  
Vol 127 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Philip A. Thompson ◽  
Constantine S. Tam ◽  
Susan M. O’Brien ◽  
William G. Wierda ◽  
Francesco Stingo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Ighv Gene ◽  
Key Points ◽  
Disease Free

Key Points FCR-treated chronic lymphocytic leukemia patients with mutated IGHV gene achieve long-term PFS, with a plateau on the PFS curve. MRD-negativity posttreatment is highly predictive of long-term PFS, particularly in patients with mutated IGHV gene.

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