AML with inv(16)/t(16;16) and high-risk cytogenetic abnormalities: atypical features and unfavorable outcome

Figures & data

Table 1. Patients’ characteristics.

	Case 1	Case 2	Case 3	Case 4	Case 5
Source	CHU-GA	CHU-GA	CHV	CHV	CHV
Gender	F	M	F	M	F
Age	43	77	76	67	56
PMH/PSH	Obesity	Smoker Polycystic kidney disease Benin Prostatic Hyperplasia Silicosis Sleep apnea	Deep Vein Thrombosis Pulmonary Embolism Hypertension Colectomy for polyposis Hypercholesterolemia	Smoker Coronary Artery Disease Chronic Obstructive Pulmonary Disease Peripheral Vascular Disease Laryngeal carcinoma (CR after surgery and radiotherapy in 2001) Epidermoid carcinoma of the palate (CR after surgery in 2006) Oropharyngeal carcinoma (CR after surgery) pulmonary epidermoid carcinoma (CR after radiotherapy, chemotherapy by carboplatin and paclitaxel)	None
Therapy related	No	Yes	No	Yes	No
Previous disease; latency period	N.A	RAEB-2; 13 months	N.A	MDS; 7 months	N.A
Previous chemotherapy	N.A	Azacitidine	N.A	Radiotherapy Carboplatin Paclitaxel Azacitidine	N.A
CBC	WBC: 53.9 G/l; Hb:10.9g/L; HCT: 34%; MCV: 85fl; Plt: 86G/l; blasts: 77%	WBC: 1.6 G/l; Hb:13.2g/L; HCT: 39%; MCV: 87fl; Plt: 116G/l; blasts: 3.5%	WBC: 1.6 G/l; Hb:7.9g/L; HCT: 0.24%; Plt: 31G/l; blasts: 4%	WBC: 18.3 G/l; Hb: 8.2g/L; HCT: 0.24l/l; MCV: 89fl; Plt: 24G/l; blasts: 79%	WBC: 1.6 G/l; Hb:10.6g/L; HCT: l/l; Plt: 97G/l; blasts: 62%
Morphology	Hypercellular marrow with hypogranular blasts (72%) and increased atypical eosinophils (12%)	Hypocellular marrow with myeloid blasts (40%), occasionally promonocytic. Eosinophils of normal morphology constituting 2.5% of nucleated cells	Hypocellular marrow with 2 sized blast population constituting 26% of nucleated cells. MPO and NSE positive. Absence of increased or atypical eosinophils	Hypercellular marrow infiltrated by 86% large blasts with agranular, occasionally vacuolated, cytoplasm and irregular nuclei, of monoblastic appearance. No excess eosinophils	65% blasts including monocytic precursors. Absence of atypical or increased eosinophils
Flow cytometry	Positive: CD2, CD13, CD33, CD117, MPO, HLA-DR, CD34 Negative: CD65	N.A	N.A	Positive: CD7, CD13, CD33, CD34, CD38, CD56, CD64, CD117, CD123, HLA DR Negative: Tdt, MPO	Positive: CD34, HLA DR, CD33, CD13, CD117, CD65, CD64, CD14 (partial), and CD4 (partial) Negative: CD2
Fusion transcript (RT-MLPA/RT-PCR)	CBFB-MYH11 Type A	CBFB-MYH11 Type A	CBFB-MYH11 Type B	CBFB-MYH11 Type F	CBFB-MYH11 Type E
High risk abnormalities	17p/TP53 deletion	Complex karyotype	Complex karyotype; Monosomal; 17p/TP53 deletion	Complex karyotype; Monosomal; 17p/TP53 deletion	Complex karyotype; Monosomal; 17p/TP53 deletion
ISCN (2016) formula	45,XX,inv(16)(p13q22)[6]/45,sl,der(12)t(12;17)(p13;q11)[14].ish inv(16)(p13)(5'CBFB+)(q22)(3'CBFB+)/der(12) (TP53-,D17Z1-)[10].nuc ish(TP53,D17Z1)x1[55/100]	45,X,-Y,inv(16)(p13q22)[5]/46,sl,+22[4]/45,sl,add(3)(q26),der(3)del(3)(p21p25)add(3)(q21),del(7)(q31q36),add(14)(q24)[5]/46,XY[6].ish add(3)(wcp3+,MECOM+),der(3)t(3;14)(q21;q?)(wcp3+,wcp14+),der(14)t(3;14)(?;q24)(wcp14+,wcp3+),inv(16)(p13)(5’CBFB+)(q22)(3’CBFB+)[10]	46,XX,del(1)(p31p36),del(4)(q21q32),der(5;17)(p10;q10),+8,t(10 ;11)(q22 ;p15),-13,der(16)inv(16)(p13 ;q22)t(13 ;16)(q14 ;q24)[6]/46,sl,del(7)(q31)[2]/46,XX[7] .nuc ish(MYH11,CBFB)x2(MYH11 con CBFBx1)[97/100]	45,XY,del(4)(q2?6q3?5),-7,-9,inv(16)(p13q22),add(17)(p1?1),+mar[10].nuc ish(MYH11,CBFBx2)(MYH11 con CBFBx1)[97/100],(TP53×1,NF1×2)[94/100]	44,XX,-5,add(16)(p13),der(17;22)(q10;q10)[12]/46,XX[2] .nuc ish(MYH11,CBFBx2)(MYH11 con CBFBx1)[75/100],(TP53×1,NF1×2)[77/100]
Additional tests	Myeloid NGS panel (43 genes): FLT3-TKD mutated FLT3-ITD negative NPM1 negative IDH1/IDH2 negative	Myeloid NGS panel (43 genes): WT1 mutated FLT3-TKD negative FLT3-ITD negative NPM1 negative IDH1/IDH2 negative	NPM1 negative FLT3 negative	FLT3-TKD negative FLT3-ITD negative NPM1 negative IDH1/IDH2 negative CKIT D816 negative	TP53 mutated (exon 10 c.1024C>T:p.Arg342Ter; variant allele frequency [VAF] 58%) KRAS mutated (exon 2 c.35G>A:p.Gly12Asp; VAF 12%)
Treatment	Cytarabine + Daunorubicin+ Gilteritinib	5-Azacitidine	5-Azacitidine	Palliative	Cytarabine +Daunorubicin
Outcome	CR not achieved. Death due to COVID-19	CR followed by relapse (60% blasts). Death one year after relapse	CR not achieved. Death due to febrile aplasia	Death	CR followed by relapse Salvage therapy: Gemtuzumab ozogamicin and cytarabine Death after 5 days due to refractory septic shock
Overall survival	1 month	15 months	6.5 months	24 days	5.5 months

CHU-GA: Centre Hospitalier Universitaire Grenoble Alpes; CHV: Centre Hospitalier de Versailles; CR: Complete Remission; N.A: Not Available; NGS: Next Generation Sequencing; RAEB: Refractory Anemia with Excess Blasts; MDS: Myelodysplastic syndrome; AML: Acute Myeloid Leukemia.