Outcome of hematopoietic stem cell transplantation in patients with atypical chronic myeloid leukemia

Koldehoff, Michael; Beelen, Dietrich W.; Trenschel, Rudolf; Steckel, Nina K.; Peceny, Rudolf; Ditschkowski, Markus; Ottinger, H.; Elmaagacli, Ahmet H.

doi:10.1038/sj.bmt.1704686

Cited by 54 publications

(33 citation statements)

References 20 publications

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“…25,26 In 9 patients with aCML, the outcome was favorable for nearly all of the patients with a median follow-up of 55 months. 27 Persistence of molecular markers after allogeneic stem transplant is associated with increased risk of disease relapse 28 and is a major cause of treatment failure in reduced intensity conditioning allogeneic stem cell transplant. In all case series evaluating survival in aCML and CNL, there is a subgroup of patients that have a more indolent clinical course with occasional survival of over 5 years.…”

Section: Clinical Management and New Directions In Acml And Cnlmentioning

confidence: 99%

What's different about atypical CML and chronic neutrophilic leukemia?

Dao

Tyner

2015

Hematology

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Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare myeloid neoplasms defined largely by morphologic criteria. The discovery of CSF3R mutations in aCML and CNL have prompted a more comprehensive genetic profiling of these disorders. These studies have revealed aCML to be a genetically more heterogeneous disease than CNL, however, several groups have reported that SETBP1 and ASXL1 mutations occur at a high frequency and carry prognostic value in both diseases. We also report a novel finding—our study reveals a high frequency of U2AF1 mutations at codon Q157 associated with CSF3R mutant myeloid neoplasms. Collectively, these findings will refine the WHO diagnostic criteria of aCML and CNL and help us understand the genetic lesions and dysregulated signaling pathways contributing to disease development. Novel therapies that emerge from these genetic findings will need to be investigated in the setting of a clinical trial to determine the safety and efficacy of targeting various oncogenic drivers, such as JAK1/2 inhibition in CSF3R-T618I–positive aCML and CNL. In summary, recent advances in the genetic characterization of CNL and aCML are instrumental toward the development of new lines of therapy for these rare leukemias that lack an established standard of care and are historically associated with a poor prognosis.

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Section: Clinical Management and New Directions In Acml And Cnlmentioning

confidence: 99%

What's different about atypical CML and chronic neutrophilic leukemia?

Dao

Tyner

2015

Hematology

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“…The clinical and morphological features of our aCML cohort are comparable to 35 chinese aCML patients, that were reported by Xubo et al (2009) except the low hemoglobin level of 7.1 g/dL in their study population. We saw moderate anemia with median hemoglobin levels of 11.4 g/dL and acceptable overall survival (Koldehoff et al, 2004). Chromosome analysis showed chromosomal abnormalities in 7/20 patients (35%), as seen in Table 1.…”

Section: Sirmentioning

confidence: 84%

Clinical course and molecular features in 21 patients with atypical chronic myeloid leukemia

Koldehoff¹,

Steckel²,

Hegerfeldt³

et al. 2011

Int J Lab Hematology

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“…2 To date, allo-SCT in the chronic phase of the disease has been the only option to improve OS. 3 No specific, recurrent cytogenetic or molecular abnormalities have been described in aCML until the recent characterization of mutations within the genes encoding the G-CSF receptor (CSF3R) and SET binding protein 1 (SETBP1) in a significant proportion of patients with aCML and chronic neutrophilic leukaemia (CNL). 4,5 Whereas the functional significance of SETBP1 mutations in aCML and CNL are not yet fully understood, the characterization of CSF3R mutations has revealed a possibility for targeted therapeutic intervention with tyrosine kinase inhibitors.…”

mentioning

confidence: 99%