Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Giebel, Sebastian; Marks, David I.; Boissel, Nicolas; Baron, Frédéric; Chiaretti, Sabina; Ciceri, Fabio; Cornelissen, Jan J.; Doubek, Michael; Esteve, Jordi; Fielding, Adele K.; Foà, Robin; Gorin, Norbert Claude; Gökbuget, Nicola; Hallböök, Heléne; Hoelzer, Dieter; Paravichnikova, Elena; Ribera, Josep‐Marǐa; Savani, Bipin N.; Rijneveld, Anita W.; Schmid, Christoph; Wartiovaara‐Kautto, Ulla; Mohty, Mohamad; Nagler, Arnon; Dombret, Hervé

doi:10.1038/s41409-018-0373-4

Cited by 111 publications

(79 citation statements)

References 60 publications

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“…We suspect under-reporting of HSCT frequency influenced the A cautious interpretation could be that since HSCT is recommended for high-risk patients, the treatment seems to counterbalance the F I G U R E 2 Overall survival in the total cohort (n = 930) in 1997-2006 and 2007-2015. Five-year overall survival improved in patients 18-45 y from 50% (95% CI 43-57) to 65% (95% CI 58-72), in patients 46-65 y from 25% (95% CI [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] to 46% (95% CI 37-55), and in patients >65 y from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P = <0.05, log-rank for pairwise comparison) [Colour figure can be viewed at wileyonlinelibrary.com] risk of relapse as previously proposed, with selection bias and transplant-related mortality as possible confounders. 37,45,46 As we noticed in our previous study of older patients, 21 there was a pronounced difference in outcome between men and women in the Ph-neg B-ALL cohort of patients 46-65 years, which we now confirm in a larger cohort and over a longer period. Inferior prognosis for males was previously reported from Poland and in historical childhood cohorts.…”

Section: Discussionsupporting

confidence: 84%

Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry

Lennmyr

Karlsson

Ahlberg

et al. 2019

European J of Haematology

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Objectives As new, effective therapies emerge for acute lymphoblastic leukaemia (ALL), the results of clinical trials need to relate to standard of care. Methods We used the population‐based Swedish ALL Registry to evaluate characteristics, treatment and long‐term outcome in 933 patients with diagnosis between 1997 and 2015. Results The median age was 53 years. The frequency of Philadelphia (Ph)‐positive leukaemia was 34% of examined B‐ALL with a peak incidence at 50‐59 years. Five‐year overall survival (OS) improved between 1997‐2006 and 2007‐2015; in patients 18‐45 years from 50% (95% CI 43‐57) to 65% (95% CI 58‐72), 46‐65 years from 25% (95% CI 18‐32) to 46% (95% CI 37‐55) and >65 years from 7% (95% CI 2.6‐11) to 11% (95% CI 5.9‐16) (P < 0.05). Men with Ph‐neg B‐ALL 46‐65 years had inferior OS compared with women (P < 0.01). Standardised mortality ratio was 5.7 (95% CI 5.0‐6.3) for patients who survived 5 years from diagnosis. In multivariable analysis, Ph‐positive disease was not associated with impaired prognosis but with lower risk of death in 2007‐2015. Conclusions In a population‐based cohort, OS has improved in adult ALL, especially for Ph‐positive disease but for middle‐aged men with Ph‐negative B‐ALL outcome was poor. Cure without late toxicity or relapse is still desired.

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Section: Discussionsupporting

confidence: 84%

Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry

Lennmyr

Karlsson

Ahlberg

et al. 2019

European J of Haematology

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“…27 High CIR rates after allo-HSCT represent a clinical issue that needs to be resolved in adverse risk AL. [3][4][5] To improve outcomes, attempts are being made to develop strategies that reduce the risk of relapse. Many technical options are now available for allo-HSCT.…”

Section: Discussionmentioning

confidence: 99%

“…Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is an established therapy that is associated with a high rate of curability for acute leukemia (AL) . However, many patients still relapse after allo‐HSCT, with common causes of death being relapse and leukemia‐associated complications . Since salvage therapy is limited for these patients, their prognosis is very poor, with a probability of long‐term survival of <20% .…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] However, many patients still relapse after allo-HSCT, with common causes of death being relapse and leukemia-associated complications. 3,4 Since salvage therapy is limited for these patients, their prognosis is very poor, with a probability of long-term survival of <20%. 5 Thus, the establishment of prevention strategies against relapse after allo-HSCT is strongly needed.…”

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confidence: 99%

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Patient‐based prediction algorithm of relapse after allo‐HSCT for acute Leukemia and its usefulness in the decision‐making process using a machine learning approach

et al. 2019

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Although allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a curative therapy for high‐risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient‐based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ‐statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision‐making process in the diversified allo‐HSCT field and be useful for preventing the relapse of leukemia.

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“…The patients with no obvious risk factors are defined standard risk (SR) and are usually excluded from treatment intensification with allogeneic HCT in first CR. This latter procedure is reserved to cases belonging to HR group, according to the risk definition adopted by each treatment protocol and study group (see below, Table 2), 21 to overcome the high likelihood of relapse associated with chemotherapy alone. However, depending on exact protocol design, selected AYA patients with intermediate/HR features can be treated with intensive chemotherapy plus maintenance regimens without allogeneic HCT in first CR.…”

Section: Risk Stratification For Risk-oriented Therapymentioning

confidence: 99%

Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population

Carobolante

Chiaretti

Skert

et al. 2020

Therapeutic Advances in Hematology

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The outstanding therapeutic progress achieved with modern pediatric regimens in childhood acute lymphoblastic leukemia (ALL) led efforts to explore whether a similar treatment approach could be equally effective and safe in older patients, starting initially with older adolescents and young adults (AYA), variably defined in different studies by an age between 15-18 and 25-39 years. Several comparative and noncomparative trials of this type have been carried out during the last two decades, enrolling thousands of patients. Almost without exception, the new strategy improved patients' outcomes compared with traditional adult treatments in B-lineage and T-lineage Philadelphia (Ph) chromosome-negative B-ALL, while the use of tyrosine kinase inhibitors (TKI) led to comparative progress in Ph+ ALL, a former high-risk subset more typically observed in older age groups. At present, highly effective pediatric-based regimens warrant 5-year survival rates of 60-70% in AYA patients. In view of these data, the same approach was progressively extended to older patients, improving the results up to 55 years of age. Issues of treatment compliance and drug-related toxicity have thus far prevented a comparable therapeutic advancement in patients aged >55 years. This critical review updates and summarizes with pertinent examples this global, positive therapeutic change, and examines how to promote further progress with new targeted therapies that include novel immuno-therapeutics and other agents developed against the many molecular dysfunctions detectable in various ALL subsets. Substantial progress is expected to occur soon, bringing AYA survival figures very close to that of children, and also to improve the outcome of ALL at all ages.

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Cited by 111 publications

References 60 publications

Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry

Survival in adult acute lymphoblastic leukaemia (ALL): A report from the Swedish ALL Registry

Patient‐based prediction algorithm of relapse after allo‐HSCT for acute Leukemia and its usefulness in the decision‐making process using a machine learning approach

Practical guidance for the management of acute lymphoblastic leukemia in the adolescent and young adult population

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