Myeloid neoplasms post cytotoxic therapy: epidemiology, pathogenesis outcomes, prognostic factors, and treatment options

Figures & data

Figure 1. Clonal evolution: from normal haematopoiesis to AML/MDS-pCT.

Table 1. Major studies that investigating the incidence of MN-pCT.

Ref	Patients (n)	Incidence	Prognosis(MN-pCT)	Latency to MN-pCT
Ref. [5]	Modern Era, 700,612 cancer patients	1619 (0.23%) were diagnosed with MN-pCT.	Median OS: 7 months
Ref. [10]	The United States, 13.7 million cancer patients (2012)	0.62 Cases/100,000, ∼10–20% of newly diagnosed MN patients	5-year OS: 10%
Ref. [24]	The United States, SEER (2001–2014)	0.13 Cases/100,000	2-year OS: 26.9%
Ref. [25]	Italian, 1999–2013	277 Patients with MN-pCT. Breast cancer (44.5%)	Median OS: 14.6 months	Median latency to MN was 5.7 years
Ref. [26]	Victoria, Australia, 2003–2014	In total, 73 of 3120 (2.3%) AML cases were classified AML-pCT. In total, 101 of 4435 (2.3%) MDS cases were classified MDS-pCT.	Median OS for AML: 6 months. Median OS for MDS: 16 months	Median latency to AML was 82 months. Median latency to MDS was 42.5 months.
Ref. [27]	Korean, 250,155 cancer patients (2009–2013)	555 (0.22%) were diagnosed with MN-pCT.	5-year OS: 29.5%	Median latency to MN-pCT was 5.37 years.
Ref. [28]	German Hodgkin Study Group, 11,952 HL patients (1993–2009)	106 (0.9%) were diagnosed with MN-pCT.	Median OS: 7.2 months	Median latency to MN-pCT was 31 months.
Ref. [29]	France, 9796 breast cancer patients (1984–2001)	30 (0.306%) were diagnosed with MN-pCT.	>1 year, 14 patients <1 month, 5 patients The longest survival _x0005_was 34 months	Median latency to MN-pCT was 33 months.

Table 2. Major cytogenetic abnormalities of MN-pCT patients.

References	Cytogenetic abnormality	MN-pCT frequency (%)	Therapeutic agent
Ref. [8]	−7/del(7q)*	49	Alkylating agent class, radiotherapy
Ref. [21]	Complex karyotype	48
Ref. [8]	del(5q)	42	Alkylating agent class
Ref. [9]	TP53	33.3	Alkylating agent class, radiotherapy
Ref. [9]	DNMT3A	8–27
Ref. [9]	ASXL1	3–17
Ref. [31]	RUNX1	11–16	Topoisomerase II inhibitor class
Ref. [31]	FLT3	8–16
Ref. [9,31]	TET2	6–14
Ref. [9,31]	NPM1	4–16
Ref. [31]	NRAS	10–13	Alkylating agent class
Ref31]	KRAS	11	Alkylating agent class
Ref. [31,32]	SRSF2	8–11
Ref. [9,31]	PTPN11	3–9
Ref. [9,31]	U2AF1	5–8
Ref. [9,31]	STAG2	5–6
Ref. [9,32]	IDH1/IDH2	3–5
Ref. [31]	CEBPA	0–5
Ref. [9,31,32]	EZH2	3–4
Ref. [8]	+8	3	Alkylating agent class
Ref. [33]	KMT2A	3	Epipodophyllotoxin
Ref. [8]	inv [16], t(16;16)	2
Ref. [8]	t(15;17)	2	Topoisomerase II inhibitor class

Table 3. Treatment options for MN-pCT patients.

Study	Study design	Phase	Patients	Results
Ref. [40]	CPX-351 vs DA	3	60–75 years of age with newly diagnosed AML-pCT	OS:9.33m vs 5.95 m; 5-year OS:18% vs8%
Ref. [41]	Azacitadine	3	≥65 years with newly diagnosed AML or AML-pCT	OS:10.4m; CR:28%
Ref. [42]	Decitabine	3	≥65 years of age with newly diagnosed AML or AML-pCT	OS:7.7m; CR:18%
Ref. [43]	Venetoclax	2	Relapsed or refractory AML or AML-pCT unfit for intensive therapy	OS:4.7m; CR:19%
Ref. [44]	Venetoclax + 5-Aza	3	newly diagnosed AML or AML-pCT	OS:14.7m; CR:66%
Ref. [45]	Venetoclax + LDAC	3	newly diagnosed AML or AML-pCT	OS:7.2m; CR:48%
Ref. [46]	Nivolumab + 5-Aza	2	Relapsed or refractory AML or AML-pCT	OS : 6.3 m; CR:33 %
Ref. [47]	Dasatinib	1b/2a	Core-binding factor AML, including 10 (11 %) patients with AML-pCT	CR:94 %, the 4-year OS rate: 52 %
Ref. [48,49]	Eprenetapopt+ 5-Aza	2	TP53-mutatetd MDS and AML	CR:56%, with deep molecular remission who achieved CR
Ref. [50]	Magrolimab +5-Aza	1b	AML unfit for intensive chemotherapy	TP53-mutated AML: CR + CRi rate was 67 % and OS was 12.9 m
Ref. [51]	Flotetuzumab	1/2	primary induction failure or early relapsed AML	CR:39 %
Ref. [53]	SNDX-5613	2	Relapsed or refractory AML With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation	CR:16%, CRp :16%

Abbreviations: AML: acute myeloid leukemia; CR: complete remission; CRi: complete remission with incomplete blood count recovery; CRp: complete remission without platelet recovery; EFS - Event-free survival; MDS: myelodysplastic syndrome; OS: overall survival; 5-Aza: Azacitidine; DA: cytarabine and daunorubicin LDAC: low-dose cytarabine.

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Data availability statement

Anonymized data are available upon reasonable request.