Minimal Residual Disease, Long-Term Outcome, and IKZF1 Deletions in Down Syndrome Acute Lymphoblastic Leukemia in a Matched Cohort Study

2021 ◽  
Author(s):  
Naomi Michels ◽  
Judith M. Boer ◽  
Amir Enshaei ◽  
Rosemary Sutton ◽  
Mats Heyman ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Cohort Study ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Matched Cohort ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Minimal Residual

Immunophenotyping to Detect Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia - Feasibility and Prognostic Significance.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4489-4489
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Krystyna Jagoda ◽  
Malgorzata Krawczyk-Kulis ◽  
Beata Stella-Holowiecka ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Antigen Expression ◽  
Term Outcome ◽  
Long Term Outcome ◽  
B Lineage ◽  
Minimal Residual

Abstract Although well documented for pediatric patients, the prognostic value of minimal residual disease (MRD) detected with the use of immunophenotyping has not been established for adults with acute lymphoblastic leukemia (ALL) so far. With the use of standard “quadrans” analysis based on evaluation of the number of blasts bearing atypicial antigen combinations, the method may be applied to the majority of T-derived and only approximately half of B-lineage ALL. In this study we tested the feasibility and prognostic significance of a new “empty spaces” method taking into account the individual antigen expression pattern for each blast cell tested. The “forbidden” gates were established with the use of triple staining by comparison with the pattern obtained for healthy volunteer bone marrow donors. At least two antigen combinations were tested for each patient. MRD was evaluated after induction and after consolidation therapy. Only patients who achieved complete remission after a single course of induction were analysed with regard to the impact of MRD on long-term outcome. Thirty adult ALL patients (B-lineage n=24, T-lineage n=6) were included in the study. For all cases it was possible to determine unique antigen expression pattern and to monitor MRD with the use of immunophenotyping at the level of 1/1000 cells. MRD was detected in 8/30 patients after induction and in 7/28 patients after consolidation tharapy (two patients relapsed during consolidation). For 11/30 patients the MRD resulted positive at least once. At 20 months the relapse rate equaled 53% for patients with MRD detected after induction or consolidation and 28% for those with MRD always negative (p=0.08). The difference was more pronounced for patients with B-lineage ALL (67% vs. 26%, p=0.02). A single MRD evaluation after induction therapy had no significant prognostic value for the risk of relapse whereas there was a trend for higher relapse rate in B-lineage ALL patients with positive MRD after completion of consolidation therapy compared to those MRD-negative at that time-point (75% vs. 32%, p=0.06). Results of the study prove the feasibility of immunophenotypic MRD evaluation in ALL. “Empty spaces” in addition to the standard “quadrans” analysis allows monitoring of the vast majority of patients regardless the immune subtype. Even with a small number of cases we were able to demonstrate its prognostic value for long-term outcome of adults with ALL.

Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00

2010 ◽  
Vol 28 (22) ◽  
pp. 3644-3652 ◽  
Author(s):  
Renato Bassan ◽  
Giuseppe Rossi ◽  
Enrico M. Pogliani ◽  
Eros Di Bona ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Adult Patients ◽  
Negative Group ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Positive Group ◽  
Disease Free

Purpose Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

Time-Sequenced G-CSF (Lenograstim) for the Treatment of Adult Acute Lymphoblastic Leukemia - Seven Year Follow-Up of the Polish Adult Leukemia Group 4–96 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2733-2733
Author(s):  
Sebastian Giebel ◽  
Jerzy Holowiecki ◽  
Malgorzata Krawczyk-Kulis ◽  
Slawomira Kyrcz-Krzemien ◽  
Andrzej Hellmann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Chemotherapy Protocol ◽  
Adult Leukemia ◽  
Leukemia Group

Abstract The goal of the study was to evaluate long-term outcome of patients treated within 4–96 trial by the Polish Adult Leukemia Group (PALG). Sixty four patients with newly diagnosed acute lymphoblastic leukemia (ALL) (median age 26 years, range 16–58) were randomly assigned to receive chemotherapy alone (n=31) or chemotherapy and glucosylated G-CSF (lenograstim) (n=33). Both groups were well-balanced in terms of age, initial WBC, immunophenotype and bcr/abl positivity. Induction therapy consisted of epirubicin+vincristin (Epi/Vcr) on days 1, 8, 15, 22, prednisone on days 1–28, L-asparaginase 8 doses starting from day 13; consolidation treatment included twice methotrexate+etoposide (Mtx/Vep), twice high dose cytarabine and cyclophosphamide (HDAraC/Ctx), CNS irradiation and intrathecal Mtx. In T-derived ALL, additional HDAraC/Ctx was administered instead of the first Mtx/HDAraC. During induction patients received G-CSF 150 μg/m2 sc. on days 2–6, 9–13, 16–20, 23-until the neutrophil recovery >1.0x109/L, starting 36 hours after Epi/Vcr, finishing 48 hours before the next dose; in consolidation - following each HDAraC/Ctx course on days 5–16. High risk patients having a donor were performed allogeneic hematopoietic cell transplantation in first complete remission, whereas those without a donor were given autologous transplant. At seven years the overall survival rate equalled 42% for G-CSF group and 24% for the controls (p=0.11). There was also a trend to higher probability of leukemia-free survival in advantage of patients receiving the cytokine (38% vs. 20%, p=0.17). The above differences might have resulted from: 1) Higher CR rate in the G-CSF group compared to the controls (94% vs. 87%), 2) Better adherence to the chemotherapy protocol (faster completion of induction-consolidation programme by 19 days, p=0.005, less dose reductions or delays), which in turn might have influenced the risk of relapse. We conclude that time sequenced G-CSF administration may improve long-term outcome of adult ALL patients although the study including larger population is required to confirm this hypothesis.

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