A prognostic scoring system for adult patients less than 60 years of age with acute lymphoblastic leukemia in first relapse

2009 ◽  
Vol 50 (7) ◽  
pp. 1126-1131 ◽  
Author(s):  
Anjali Advani ◽  
Tao Jin ◽  
Brian Bolwell ◽  
Edward Copelan ◽  
Mikkael Sekeres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Scoring System ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
First Relapse

Outcome After First Relapse In Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3084-3084
Author(s):  
Shinichi Kako ◽  
Heiwa Kanamori ◽  
Naoki Kobayashi ◽  
Akio Shigematsu ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Median Duration ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Salvage Chemotherapy ◽  
Adult Patients ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
First Relapse

Abstract Abstract 3084 With modern intensive chemotherapy, 78% to 93% of adult patients with acute lymphoblastic leukemia (ALL) achieve complete remission (CR). However, the disease-free survival rate is only 30% to 40% due to the high rate of relapse. A part of relapsed patients can achieve second remission (CR2) with salvage therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) in CR2 will be the only curative strategy. Prognosis after relapse in adult patients with ALL is considered to be extremely poor, but reports as to the outcome after relapse have been limited. To elucidate the outcome of relapsed patients and prognostic factors after relapse, we retrospectively collected and analyzed clinical data from 69 institutions in Japan on patients with Philadelphia-chromosome (Ph) negative ALL, aged 16–65 years, who relapsed after first CR (CR1) between 1998 and 2008. A total of 332 patients were included in this study. The median age of them was 35 years, and 165 patients were male. Median duration of CR1 was 290 days (range 15–7162 days), and median follow-up time after relapse was 319 days (range 3–3689 days). Fifty-eight and 4 of them relapsed after allogeneic and autologous HSCT in CR1, respectively. The overall survival (OS) rate was not significantly different between patients who relapsed after allogeneic HSCT in CR1 and those who relapsed after chemotherapy only (50.0% vs. 43.4% at 1 year and 10.6% vs. 16.3% at 5 year, respectively). Among 270 patients who relapsed after chemotherapy only, 234 patients received salvage chemotherapy after relapse, and 123 patients achieved CR2 (52.5%). Sixty-two patients out of those 123 patients underwent allogeneic HSCT in CR2. Median duration between the achievement of CR2 with salvage chemotherapy and allogeneic HSCT in CR2 was 76 days. OS rate was significantly better in patients who underwent allogeneic HSCT in CR2 following salvage chemotherapy than those who did not (74.1% vs. 55.1% at 1 year and 44.7% vs. 11.6% at 5 year, respectively) by a landmark analysis limiting patients who were surviving without disease at 76 days after the achievement of CR2. In multivariate analysis of factors that included allogeneic HSCT in CR2 following salvage chemotherapy as a time-dependent covariate, lower white blood cell count at relapse (less than 10000/μl) and allogeneic HSCT in CR2 were associated with better OS rate among patients who achieved CR2 following salvage chemotherapy. Forty-six patients underwent allogeneic HSCT in non-CR after receiving salvage chemotherapy. A part of them survived long, and 5 year OS rate was 20.9%. In conclusion, the prognosis of adult patients with relapsed Ph-negative ALL is poor. Allogeneic HSCT after first relapse could improve the prognosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Unravelling the Sequential Interplay of Mutational Mechanisms during Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 214
Author(s):  
Željko Antić ◽  
Stefan H. Lelieveld ◽  
Cédric G. van der Ham ◽  
Edwin Sonneveld ◽  
Peter M. Hoogerbrugge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Leukemic Cells ◽  
Proliferative Potential ◽  
Disease Evolution ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
First Relapse ◽  
Mutational Processes

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is characterized by clonal heterogeneity. Genomic mutations can increase proliferative potential of leukemic cells and cause treatment resistance. However, mechanisms driving mutagenesis and clonal diversification in ALL are not fully understood. In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. Based on mutation allele frequencies at diagnosis and subsequent relapses, we clustered mutations into groups and performed cluster-specific mutational profile analysis and de novo signature extraction. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity. The associated signatures SBS2 and SBS13 were present already at diagnosis, and although emerging mutations were lost in later relapses, the process remained active throughout disease evolution. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling ultraviolet light-driven DNA damage, and thiopurine-associated damage at first relapse. In conclusion, our data shows that investigation of mutational processes in clusters separated in time may aid in understanding the mutational mechanisms and discovery of underlying causes.

The ABCs of Immunotherapy for Adult Patients With B-Cell Acute Lymphoblastic Leukemia

2017 ◽  
Vol 52 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Troy Z. Horvat ◽  
Amanda N. Seddon ◽  
Adebayo Ogunniyi ◽  
Amber C. King ◽  
Larry W. Buie ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Data Extraction ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Car T Cells ◽  
Car T ◽  
American Society

Objective: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). Data Sources: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). Study Selection/Data Extraction: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified. Data Synthesis: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL. Conclusion: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.

Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1375-1382 ◽  
Author(s):  
Jan J. Cornelissen ◽  
Bronno van der Holt ◽  
Gregor E. G. Verhoef ◽  
Mars B. van 't Veer ◽  
Marinus H. J. van Oers ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Donor Group ◽  
No Donor ◽  
Sibling Donor ◽  
Standard Risk

Abstract While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (± 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.

scholarly journals Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

Haematologica ◽  
2010 ◽  
Vol 95 (4) ◽  
pp. 589-596 ◽  
Author(s):  
A. Oriol ◽  
S. Vives ◽  
J. M. Hernandez-Rivas ◽  
M. Tormo ◽  
I. Heras ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Study Group

An effective reinduction regimen for first relapse of adult acute lymphoblastic leukemia

2013 ◽  
Vol 30 (4) ◽  
Author(s):  
Ibrahim Aldoss ◽  
Vinod Pullarkat ◽  
Ravindra Patel ◽  
Kristy Watkins ◽  
Ann Mohrbacher ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Acute Lymphoblastic Leukemia ◽  
First Relapse

scholarly journals Marrow Transplants From Unrelated Donors for Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1410-1414 ◽  
Author(s):  
Jorge Sierra ◽  
Jerry Radich ◽  
John A. Hansen ◽  
Paul J. Martin ◽  
Effie W. Petersdorf ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Unrelated Donor ◽  
Effective Treatment Option ◽  
Patients At Risk ◽  
Unrelated Donors ◽  
First Relapse ◽  
Philadelphia Chromosome Positive

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% ± 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

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