Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc
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Review

Volume 11, Number 6, December 2022, pages 197-209

Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies

Figure

Figure 1.
Figure 1. Flowchart showing treatment options for patients with post-MPN AML. Patients are assessed for medical fitness, which can be represented with Eastern Cooperative Oncology Group (ECOG) performance status. Generally, patients with ECOG 0 - 1 can be considered fit. Patients with ECOG 2 - 3 are often considered unfit. Patients with ECOG 4 are considered frail. Most often fit patients are considered for clinical trials, however “unfit” are sometimes also included, and frail patients are rarely included. Median overall survival was gathered from previous clinical trials with ranges displayed. mOS: median overall survival; mo: months.

Tables

Table 1. Mutations That Are Implicated in Post-MPN AML and Have a Frequency of 15% of Higher
 
Frequency in MPNFrequency in sAMLReference
MPN: myeloproliferative neoplasms; sAML: secondary AML; post-MPN AML: post-myeloproliferative neoplasm acute myeloid leukemia; PV: polycythemia vera; ET: essential thrombocytosis; PMF: primary myelofibrosis.
Epigenetic regulators
  TET210-20%21%Grinfeld et al, 2018 [31]
  DNMT3A5-10%18%Stegelmann et al, 2011 [33]
  IDH1/21-4% PMF21%Tefferi et al, 2010 [35]
< 2% in PV and ET
  ASXL125% PMF25%Vallapureddy et al, 2019 [30]
1-3% in PV and ET
Transcriptional regulators
  TP53< 5%10-20%Grinfeld et al, 2018 [31]
  MDM4< 1%18%Harutyunyan et al, 2011 [32]
RNA splicing
  SRSF22% PMF18.90%Zhang et al, 2012 [34]

 

Table 2. A Comparison of Median Overall Survival Among Different Treatment Regimens and Studies
 
StudyNmOS (months) post-MPN AMLNotes/specific treatment
mOS: median overall survival; post-MPN AML: post-myeloproliferative neoplasm acute myeloid leukemia; HMA: hypomethylating agent; PFS: progression-free survival; HSCT: hematopoietic stem cell transplantation.
Induction chemotherapy
  Mesa et al, 2005 [10]243.9Cytarabine, mitoxantrone, gemtuzumab
  Tam et al, 2008 [48]366
  Passamonti et al, 2010 [4]85.6
  Kennedy et al, 2013 [49]139.4
  Badar et al, 2015 [50]357.6No significant difference between induction and decitabine
  Venton et al, 2017 [51]348.3
  Lancet et al, 2021 [47]1565.95
  Lancet et al, 2021 [47]1539.33Liposomal daunorubicin and cytarabine
  Gangat et al, 2021 [52]698
  Castillo Tokumori et al, 2022 [53]2811.4This number is higher due to HSCT after chemotherapy
  Castillo Tokumori et al, 2022 [53]154.9Chemotherapy alone
Non-induction chemotherapy
  Mesa et al, 2005 [10]482.9Vincristine, melphalan, cytarabine (low-dose), etoposide, etc.
  Tam et al, 2008 [48]127
  Passamonti et al, 2010 [4]82.5
HMA +/- venetoclax
  Thepot et al, 2010 [54]268Azacytidine
  Kennedy et al, 2013 [49]156.6
  Andriani et al, 2015 [55]199.9Azacytidine
  Badar et al, 2015 [50]216.9Decitabine
  Venton et al, 2017 [51]117.9Azacytidine
  Mascarenhas et al, 2020 [56]259.5Decitabine and ruxolitinib
  Gangat et al, 2021 [52]328
  Gangat et al, 2021 [52]265.5HMA + venetoclax
  Castillo Tokumori et al, 2022 [53]284.7HMA alone
Supportive care
  Mesa et al, 2005 [10]192
  Tam et al, 2008 [48]191.5
  Passamonti et al, 2010 [4]72.5
  Venton et al, 2017 [51]281.8
  Castillo Tokumori et al, 2022 [53]190.8
Stem cell transplant
  Tam et al, 2008 [48]873% survival at 31months follow-up
  Passamonti et al, 2010 [4]1> 70-day survival
  Cherington et al, 2012 [9]8PFS 74.9% at 2 years
  Kennedy et al, 2013 [49]1747
  Badar et al, 2015 [50]74/7 died in the first 100 days
  Venton et al, 2017 [51]924.2
  Gangat et al, 2021 [52]6Received HSCT after venetoclax + HMA
  Castillo Tokumori et al, 2022 [53]1340.8
All patients with LT of MPN
  Mesa et al, 2005 [10]912.7
  Tam et al, 2008 [48]745
  Tefferi et al, 2017 [44]4103.6No improvement in the last 15 years