CXCR4 is a valuable poor prognostic marker for chronic lymphocytic leukemia: its higher level of expression is associated with inferior response to therapy and lower disease-free survival

2021 ◽  
Vol 46 (2) ◽  
pp. 99
Author(s):  
MostafaK.El Razzaz ◽  
Inas Asfour ◽  
WalaaA Elsalakawy ◽  
MohamedT.H Sallam
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Marker ◽  
Disease Free Survival ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Disease Free

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)

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 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.

The AST/ALT Ratio Is an Independent Prognostic Marker for Disease-free Survival in Stage II and III Colorectal Carcinoma

2021 ◽  
Vol 41 (1) ◽  
pp. 429-436
Author(s):  
LUKAS SCHEIPNER ◽  
MARIA ANNA SMOLLE ◽  
DOMINIK BARTH ◽  
FLORIAN POSCH ◽  
MICHAEL STOTZ ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Prognostic Marker ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Independent Prognostic Marker ◽  
Disease Free

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.

Outcomes of multivisceral resection of gastric gastrointestinal stromal tumors.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 91-91
Author(s):  
Sabha Ganai ◽  
Mitchell Posner ◽  
Vivek N. Prachand ◽  
John C. Alverdy ◽  
Eugene A. Choi ◽  
...  
Keyword(s):  
Tumor Size ◽  
Gastrointestinal Stromal Tumors ◽  
Disease Free Survival ◽  
Multivisceral Resection ◽  
Response To Therapy ◽  
Hospital Length Of Stay ◽  
Free Survival ◽  
Stromal Tumors ◽  
Gastric Gists ◽  
Disease Free

91 Background: Despite the recent introduction of imatinib and laparoendoscopic techniques to the management of gastric gastrointestinal stromal tumors (GISTs), outcomes remain uncertain in the setting of multivisceral involvement. Methods: We conducted a retrospective review of 69 consecutive patients who underwent resection of gastric GISTs from October 2002 through August 2011. Median follow-up was 19 months (interquartile range [IQR] 4-37). Results: Patients were 51% female, with a mean age of 65 ± 13 years and BMI of 30 ± 8 kg/m2. Patients undergoing multivisceral resection (n=13) had a longer interval from diagnosis to surgery (7.4 [IQR 1.9 – 15.0] vs. 1.3 [IQR 0.7-3.5] months, p<0.01), greater use of neoadjuvant imatinib (62% vs. 4%, p<0.001), and greater preoperative tumor size (12 ± 8 vs. 4 ± 3 cm, p<0.001) in comparison to gastric-only resections (n=56). Patients were less likely to be managed laparoscopically (8% vs. 71%, p<0.001), had a longer operative time (286 ± 92 vs. 152 ± 65 min, p<0.001), and were less likely to be R0 (69% vs. 98%, p<0.001). While patients undergoing multivisceral resection were more likely to have a pathological complete response to therapy (23% vs. 0, p<0.01), they were also more likely to have metastatic disease present (31% vs. 0, p<0.01). Hospital length of stay was greater (median 8 [IQR 7-9] vs. 3 [IQR 2-6] days, p<0.001). There were no significant differences in grade or mitotic index between groups, or in the use of adjuvant imatinib (54% vs. 23%). Overall survival was less in patients undergoing multivisceral resection (63% vs. 86% at 3 years, p<0.05), as was disease-free survival (52% vs. 71% at 3 years, p<0.05). Median disease-free survival was 50 and 66 months, respectively (p<0.01). Controlling for tumor size, grade, resection status, and the use of neoadjuvant imatinib, multivisceral resection was an independent predictor of disease-free survival (p<0.05). Conclusions: Multivisceral involvement is associated with tumors of greater size, and despite an increased use of neoadjuvant imatinib, it is associated with poor outcome for patients with gastric GISTs.

Generation of adaptive HER2-specific immunity in HER2 breast cancer patients by addition of trastuzumab to chemotherapy in the adjuvant setting: NCCTG (Alliance) study N9831.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
Keith L. Knutson ◽  
Edith A. Perez ◽  
Karla V. Ballman ◽  
Courtney L. Erskine ◽  
Nicholas Fox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Adjuvant Setting ◽  
Free Survival ◽  
Specific Immunity ◽  
Her2 Breast Cancer ◽  
Disease Free

522 Background: In the adjuvant setting, patients with HER2 breast cancer treated with trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induces HER2-specific antibodies which correlate with response to therapy in patients with HER2+ metastatic breast cancer. It remained unclear from those studies, however, whether the HER2-specific immunity played a role and if antibody immunity was associated with improved disease free survival in the adjuvant setting. In the present study, we addressed these questions by analyzing sera samples from a subset of patients enrolled in the NCCTG adjuvant trial, N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. Methods: Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831 (22 Arm A; 14 Arm B, and 14 Arm C). Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and presented as an index (>0.2 was considered a positive response). Results: Prior to therapy, across all three arms, N9831 patients had similar mean HER2 IgG levels (0.19 units in Arm A, 0.14 in Arm B, and 0.23 in Arm C, P=0.85). Following treatment, the mean levels of antibodies increased in Arm B to 0.35 units and in Arm C to 0.56 units and were higher (p<0.001) than in Arm A where levels did not increase. The proportion of patients who demonstrated antibody immunity increased by 9% in Arm A, 50% in Arm B and 28% in Arm C (P=0.026). Although the event rate was low in this cohort, Cox modeling suggested that larger increases in antibodies were associated with improved disease free survival (HR=0.23; p=0.04). Conclusions: These results show that the increased antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant and results from the inclusion of trastuzumab. The findings may have important implications for improving treatment outcomes in patients treated with trastuzumab.

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.

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