Table 1 Clinicopathologic features of 4 cases of myeloid neoplasm in setting of sickle cell disease
Item | Case 1 | Case 2 | Case 3 | Case 4 |
|---|---|---|---|---|
Sex | Male | Female | Female | Male |
Age (year) | 34 | 37 | 59 | 27 |
Hemoglobin type | S/β0 | SS | SC | SS |
Clinical history | Minor sickling crisis, priapism, arterial aneurysm, intracranial bleeding | Frequent sickling crisis since infancy, aggravated with pregnancy (three times); substance abuse, Parvovirus IGG + , EBV IGM + | HHV8 + DLBCL 1 year before MN | Rare sickling crisis, myocardial infarction, Moyamoya disease, HIV + 3 years before MN |
Presentation at diagnosis of MN | Progressive anemia, thrombocytopenia | Progressive thrombocytopenia, fever | Leukocytosis with monocytosis | Leukocytosis |
Treatment for HbSS or equivalent Hb | HU (400 mg/day), matched HSCT, exchanged transfusion | Exchanged transfusion, supportive | HU (500–1500 mg/day), exchanged transfusion | Exchange transfusion, multiple medications |
Interval from treatment to MN (years) | 9 years after HU; 7 years after HSCT; | N/A | > 20 years | N/A |
CBC (WBC/Hb/MCV/PLT) | 4.1/7.8/69/29 | 19/5.6/97/50 | 39.9/7.6/80/203 | 34.6/9.4/86/222 |
Blood smear findings other than RBC morphology | No blasts | Left-shifted neutrophilia, no blasts | Leukoerythroblastosis, monocytosis, 3% blasts | 37% blasts |
Marrow cellularity | 95% | 90% | 85% | 95% |
Dysplasia | Erythroid, megakaryocytic | Megakaryocytic | Trilineage | Erythroid |
Marrow blasts (%) | 2 | 5 | 5 | 72 |
Immunophenotype | N/A | N/A | Myeloid/monocytic | Myeloid/monocytic |
TP53 | 2–4% | 30% | 35–40% | Majority of blasts |
Karyotype | 45,XY,-2,der(7)(2pter- > 2p11.2::7p11.1- > 7q22::?2q11.2- > 2qter),inv(9)(p11q13)c[18]/45,idem,?del(20)(q11.2q13.1)[2] | 48,XX,add(1)(p22), + del(1)(q31),del(5)(q15q33),der(6)?t(3;6)(p21;p21),−17, + 3~ 5mar[cp3]/46,XX[1] | 44~ 45,XX,del(4)(p14p16),der(5;7)(p10;p10),−15,−16,add(18)(q21), + 1~ 2mar[10]/44~ 45,idem,add(12)(p13)[6]/43~ 44,idem, + add(4)(p14),-del(4)(p14p16),−12[4] | 49,XY,t(6;11)(q27;q23), + 3, + 19, + 21[20] |
Interphase FISH | 7q- (76%) | 5q- (24%), additional 5p + (10%) | 5q-(92%), 7q-(93%), BCR/ABL(−) | KMT2A (11q23) (55%)* |
Molecular tests | Chimerism 1 year after HSCT, gradual decrease in donor fraction (4 years), and complete loss of graft 2 years before MN | TP53(+ ; VAF = 0.224), BCR/ABL(−), JAK2(−), CALR(−), MPL(−) | TP53(+ ; VAF = 0.907), JAK2(−), CALR(−), MPL(−) | TP53(−)*, FLT3(−), IDH1/2(−) |
Diagnosis type | MDS-MLD | MDS/MPN-U | MDS/MPN (CMML) | AML-MRC |
Treatment for myeloid neoplasm | Busulfan/fludarabine/ATG, HSCT (matched sibling) | Lenalidomide (5 mg/day), IVIG (5 days), prednisone (60 mg/day) | Decitabine | 7 + 3, then 2 + 5, HSCT |
Follow-up (mo) | 21 | 5 | 2 | 7 |
Outcome | Alive | Alive | Died | Died |
Additional note | Donor cells (> 98%); EBV copies (> 4000); FISH: (−)7q- | Persistent MN, with plan for HSCT | Systemic dissemination, multiorgan failure | Loss of graft with relapse 3 months before death |
