Table 4. Rare immunophenotypes of LS and... | American Society of Hematology

Table 4.

Rare immunophenotypes of LS and lineage drift

Case ID	Case overview at diagnosis	Cytogenetics	Prior therapy	Time from most proximal immunotherapy to LS (mo)	Retained cytogenetics/molecular	Retained BCR rearrangements	Flow at time of LS/drift	Treatment of LS/lineage drift (number of therapy lines)	Reversion back to B-ALL at any time after LS	Clinical outcome	Time from LS to death or date of last f/u (mo)
Rare LS cases
E-008	14.2-yo F T-ALL → AML	KMT2Ar Inv(11)(q13q23) 46∼47,XX,del(6)(q13q23),inv(11)(q13q23),i(17)(q10),+mar[cp6]/46,XX	Blinatumomab: N Inotuzumab: N CAR: N HSCT: N Other: daratumumab∗	0.2	Y	UNK	B-cell: N/A T-cell: CD7 Myeloid: CD13, CD33, CD15, CD117, MPO Other: CD45, CD11b, CD16, CD56, CD34, HLA-DR, CD52, CD58, CD4, CD71	Venetoclax, azacytidine → no CR CPX-351/GO → no CR Decitabine, vorinostat → no CR	N/A	Died from disease	4.8
E-027	37.7-yo M T-ALL → AML	EZH2 p.S438Cfs∗2, BCL2 p.P65Rfs∗31, PRPF40B c.496+1G>A, PRDM1 p.Q530X	Blinatumomab: N Inotuzumab: N CAR: Y (CD7)∗ HSCT: Y Other: daratumumab	9.0	UNK	UNK	B-cell: N/A T-cell: N/A Myeloid: CD33, CD117, CD123 Other: CD99, CD38, TdT, HLA-DR	Venetoclax, ARA-C → CR HSCT	N/A	Died from septic shock after HSCT	2.4
E-058	14-yo F B-ALL →MPAL (T/myeloid)	45,X,- X,add(4)(p14),der(8;12)(q10;q10),?add(9)(p13), -16, ?add(21)(q22),+2mar[12]/46,XY[8]. Positive for loss of the CDKN2A locus (also known as p16) in 91.5% of cells. t(12; 21) ETV6-RUNX1 gene rearrangement in 99.5% of cells.	Blinatumomab: Y∗ Inotuzumab: N CAR: Y HSCT: Y Other: N/A	3.3	Y	UNK	B-cell: N/A T-cell: CD3 Myeloid: CD33, CD117, MPO Other: CD34, CD133	Venetoclax, ARA-C → CR Fludarabine, ARA-C → no CR GO → UNK Venetoclax, decitabine → no CR Dexamethasone, VCR, asparaginase → UNK Etoposide → UNK	N	Died from disease	10.8
E-060	30.5-yo M T-ALL → AML	46,XY; FISH showed tetrasomy of chromosome 6 and 21 in 8.5%, and 1-2 extra signals/copies on chromosome 8, 8, 11, and 22 in 5%-13.5%	Blinatumomab: N Inotuzumab: N CAR: Y (allo-CD7)∗ HSCT: N Other: N/A	1.2	N†	UNK	B-cell: N/A T-cell: N/A Myeloid: CD13, CD33, CD123, MPO Other: CD34, HLA-DR	Venetoclax, azacytidine → no CR	N/A	Died from disease	3.6
E-073	18.2-yo M B-ALL → plasmablastic lymphoma	t(14;18) as well as der(4)t(1;4), microarray results had several copy-number variations including focal losses involving IKZF1 and PAX5, Ph-like phenotype	Blinatumomab: N Inotuzumab: Y CAR: Y∗ HSCT: N Other: N/A	3.7	UNK†	Y	Tissue biopsy B-cell: N/A T-cell: N/A Myeloid: N/A Other: CD138, MUM1, CD43, CD56, vimentin, CD117, EMA	DA-EPOCH → PR/near CR HSCT	N	Alive in CR	38.4
Lineage drift
E-009	0.4-yo M MPAL	Normal at diagnosis	Blinatumomab: N Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	1	N	Y	B-cell: partial CD19, partial CD79a T-cell: CD7 Myeloid: variable CD64, partial CD117, partial CD15, CD33, partial CD11c Other: CD34, CD38, HLA-DR	Decitabine, ARA-C, etoposide, daunorubicin, GO → no CR Blinatumomab → CR HSCT	Y	Died from disease	14.4
E-039	12.6-yo F B-ALL	KMT2Ar t(11;19)(q23.3;p13.3)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	6	Y	Y	First population B-cell: N/A T-cell: N/A Myeloid: CD123, CD117 Other: CD38, CD58, CD45, HLA-DR Second population B-cell: CD19, CD79a, iCD22 T-cell: N/A Myeloid: CD33, CD15 Other: CD45, CD38, CD58	hAM24 → no CR HSCT with infusion of haploidentical CD19/CD22 CAR T cells	Y	Died from relapse of B-ALL	8.4
E-040	14-d-old F MPAL	KMT2Ar t(4;11)(q21.3-q22.1;q23.3)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: N Other: N/A	0.7	Y	N	First population B-cell: CD10, CD19, CD20 T-cell: N/A Myeloid: N/A Other: CD58, CD45, CD34, CD38 Second population B-cell: N/A T-cell: N/A Myeloid: CD64, CD33, CD14, Lysozyme Other: CD45	Palliative care	N	Died from disease	9 days
E-046	6.4-yo M B-ALL	KMT2Ar t(4;11)(q21.3-q22.1;q23.3)	Blinatumomab: N Inotuzumab: Y∗ CAR: N HSCT: N Other: N/A	0.2	Y	UNK	First population B-cell: CD19, CD79a, CD22 T-cell: N/A Myeloid: N/A Other: CD34, NG2 Second population B-cell: CD19 T-cell: N/A Myeloid: CD33 Other: CD45	Blinatumomab → no CR	Y	Died from relapse of B-ALL	2.4
E-047	0.4-yo F B-ALL	KMT2Ar t(5q31;11q23)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	0.3	Y	UNK	B-cell: sCD19low T-cell: N/A Myeloid: CD33, CD14, CD15, CD64 Other: CD11b	Discontinuation of blinatumomab, DNX-FLA, stem cell boost→ no CR LD ARA-C, blinatumomab, RT to EMD → no CR	Y	Died from original B-ALL (chloromas)	3
E-051	7.1-yo M B-ALL	KMT2Ar‡ t(9;11)(q22;q23)	Blinatumomab: Y Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	2	Y	Y	B-cell: CD10, CD22, CD24, CD20T-cell: N/A Myeloid: CD13, CD33 Other: CD58, CD38, CD34, CD9	Inotuzumab → no CR Prednisone, cyclophosphamide, ARA-C → UNK Cappizzi MTX, dexamethasone, VCR → UNK	Y	Died from intracranial hemorrhage secondary to relapsed disease	4.8
E-052	10-yo F B-ALL	Amplification of RUNX1 46,X,t(X;12)(p11 .2;q24.1),-21, +mar1[10J/46,idem,add(1)(q22), - 8,add(15)(q11 .2),−mar1, +mar2 ,+r[3]/46,XX[12] FISH: 72% positive for gains of AML1 (5-15 copies)	Blinatumomab: Y Inotuzumab: N CAR: Y∗ HSCT: Y Other: N/A	7.2	Y (with evolution)	Y	B-cell: CD10, CD22, CD24 T-cell: N/A Myeloid: CD13, CD33 Other: CD58, CD38, CD9	Inotuzumab → CR	N	Died from septic shock	3.6
E-055	1-d-old M MPAL	KMT2Ar t(11;14;19)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: N Other: N/A	2	Y	Y	B-cell: CD19 T-cell: N/A Myeloid: CD33 Other: CD45, HLA-DR, CD38, CD133, CD9, CD40	HD ARA-C/asparaginase → no CR Hydroxyurea, steroids, then menin inhibitor (SNDX-5613) → CR	N	Alive with disease	4.8
E-082	17.1-yo M B-ALL	Hypodiploid	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	8.0	UNK	N	B-cell: CD10, CD20, CD79a T-cell: N/A Myeloid: CD33 Other: TdT, CD45, CD34, HLA-DR	VCR, asparaginase, dexamethasone → no CR VP16, ARA-C, asparaginase, mercaptopurine → no CR Inotuzumab → CR	N	Died from disease	6
E-091	11-d-old F B-ALL	KMT2Ar t(4;11)	Blinatumomab: N Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	2.4	Y	UNK	B-cell: CD19 T-cell: CD7 Myeloid: CD15, CD64 Other: CD9, CD38, CD34, CD58, HLA-DR	Venetoclax, azacytidine → no CR	N	Died from disease	1.2

Case ID	Case overview at diagnosis	Cytogenetics	Prior therapy	Time from most proximal immunotherapy to LS (mo)	Retained cytogenetics/molecular	Retained BCR rearrangements	Flow at time of LS/drift	Treatment of LS/lineage drift (number of therapy lines)	Reversion back to B-ALL at any time after LS	Clinical outcome	Time from LS to death or date of last f/u (mo)
Rare LS cases
E-008	14.2-yo F T-ALL → AML	KMT2Ar Inv(11)(q13q23) 46∼47,XX,del(6)(q13q23),inv(11)(q13q23),i(17)(q10),+mar[cp6]/46,XX	Blinatumomab: N Inotuzumab: N CAR: N HSCT: N Other: daratumumab∗	0.2	Y	UNK	B-cell: N/A T-cell: CD7 Myeloid: CD13, CD33, CD15, CD117, MPO Other: CD45, CD11b, CD16, CD56, CD34, HLA-DR, CD52, CD58, CD4, CD71	Venetoclax, azacytidine → no CR CPX-351/GO → no CR Decitabine, vorinostat → no CR	N/A	Died from disease	4.8
E-027	37.7-yo M T-ALL → AML	EZH2 p.S438Cfs∗2, BCL2 p.P65Rfs∗31, PRPF40B c.496+1G>A, PRDM1 p.Q530X	Blinatumomab: N Inotuzumab: N CAR: Y (CD7)∗ HSCT: Y Other: daratumumab	9.0	UNK	UNK	B-cell: N/A T-cell: N/A Myeloid: CD33, CD117, CD123 Other: CD99, CD38, TdT, HLA-DR	Venetoclax, ARA-C → CR HSCT	N/A	Died from septic shock after HSCT	2.4
E-058	14-yo F B-ALL →MPAL (T/myeloid)	45,X,- X,add(4)(p14),der(8;12)(q10;q10),?add(9)(p13), -16, ?add(21)(q22),+2mar[12]/46,XY[8]. Positive for loss of the CDKN2A locus (also known as p16) in 91.5% of cells. t(12; 21) ETV6-RUNX1 gene rearrangement in 99.5% of cells.	Blinatumomab: Y∗ Inotuzumab: N CAR: Y HSCT: Y Other: N/A	3.3	Y	UNK	B-cell: N/A T-cell: CD3 Myeloid: CD33, CD117, MPO Other: CD34, CD133	Venetoclax, ARA-C → CR Fludarabine, ARA-C → no CR GO → UNK Venetoclax, decitabine → no CR Dexamethasone, VCR, asparaginase → UNK Etoposide → UNK	N	Died from disease	10.8
E-060	30.5-yo M T-ALL → AML	46,XY; FISH showed tetrasomy of chromosome 6 and 21 in 8.5%, and 1-2 extra signals/copies on chromosome 8, 8, 11, and 22 in 5%-13.5%	Blinatumomab: N Inotuzumab: N CAR: Y (allo-CD7)∗ HSCT: N Other: N/A	1.2	N†	UNK	B-cell: N/A T-cell: N/A Myeloid: CD13, CD33, CD123, MPO Other: CD34, HLA-DR	Venetoclax, azacytidine → no CR	N/A	Died from disease	3.6
E-073	18.2-yo M B-ALL → plasmablastic lymphoma	t(14;18) as well as der(4)t(1;4), microarray results had several copy-number variations including focal losses involving IKZF1 and PAX5, Ph-like phenotype	Blinatumomab: N Inotuzumab: Y CAR: Y∗ HSCT: N Other: N/A	3.7	UNK†	Y	Tissue biopsy B-cell: N/A T-cell: N/A Myeloid: N/A Other: CD138, MUM1, CD43, CD56, vimentin, CD117, EMA	DA-EPOCH → PR/near CR HSCT	N	Alive in CR	38.4
Lineage drift
E-009	0.4-yo M MPAL	Normal at diagnosis	Blinatumomab: N Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	1	N	Y	B-cell: partial CD19, partial CD79a T-cell: CD7 Myeloid: variable CD64, partial CD117, partial CD15, CD33, partial CD11c Other: CD34, CD38, HLA-DR	Decitabine, ARA-C, etoposide, daunorubicin, GO → no CR Blinatumomab → CR HSCT	Y	Died from disease	14.4
E-039	12.6-yo F B-ALL	KMT2Ar t(11;19)(q23.3;p13.3)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	6	Y	Y	First population B-cell: N/A T-cell: N/A Myeloid: CD123, CD117 Other: CD38, CD58, CD45, HLA-DR Second population B-cell: CD19, CD79a, iCD22 T-cell: N/A Myeloid: CD33, CD15 Other: CD45, CD38, CD58	hAM24 → no CR HSCT with infusion of haploidentical CD19/CD22 CAR T cells	Y	Died from relapse of B-ALL	8.4
E-040	14-d-old F MPAL	KMT2Ar t(4;11)(q21.3-q22.1;q23.3)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: N Other: N/A	0.7	Y	N	First population B-cell: CD10, CD19, CD20 T-cell: N/A Myeloid: N/A Other: CD58, CD45, CD34, CD38 Second population B-cell: N/A T-cell: N/A Myeloid: CD64, CD33, CD14, Lysozyme Other: CD45	Palliative care	N	Died from disease	9 days
E-046	6.4-yo M B-ALL	KMT2Ar t(4;11)(q21.3-q22.1;q23.3)	Blinatumomab: N Inotuzumab: Y∗ CAR: N HSCT: N Other: N/A	0.2	Y	UNK	First population B-cell: CD19, CD79a, CD22 T-cell: N/A Myeloid: N/A Other: CD34, NG2 Second population B-cell: CD19 T-cell: N/A Myeloid: CD33 Other: CD45	Blinatumomab → no CR	Y	Died from relapse of B-ALL	2.4
E-047	0.4-yo F B-ALL	KMT2Ar t(5q31;11q23)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	0.3	Y	UNK	B-cell: sCD19low T-cell: N/A Myeloid: CD33, CD14, CD15, CD64 Other: CD11b	Discontinuation of blinatumomab, DNX-FLA, stem cell boost→ no CR LD ARA-C, blinatumomab, RT to EMD → no CR	Y	Died from original B-ALL (chloromas)	3
E-051	7.1-yo M B-ALL	KMT2Ar‡ t(9;11)(q22;q23)	Blinatumomab: Y Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	2	Y	Y	B-cell: CD10, CD22, CD24, CD20T-cell: N/A Myeloid: CD13, CD33 Other: CD58, CD38, CD34, CD9	Inotuzumab → no CR Prednisone, cyclophosphamide, ARA-C → UNK Cappizzi MTX, dexamethasone, VCR → UNK	Y	Died from intracranial hemorrhage secondary to relapsed disease	4.8
E-052	10-yo F B-ALL	Amplification of RUNX1 46,X,t(X;12)(p11 .2;q24.1),-21, +mar1[10J/46,idem,add(1)(q22), - 8,add(15)(q11 .2),−mar1, +mar2 ,+r[3]/46,XX[12] FISH: 72% positive for gains of AML1 (5-15 copies)	Blinatumomab: Y Inotuzumab: N CAR: Y∗ HSCT: Y Other: N/A	7.2	Y (with evolution)	Y	B-cell: CD10, CD22, CD24 T-cell: N/A Myeloid: CD13, CD33 Other: CD58, CD38, CD9	Inotuzumab → CR	N	Died from septic shock	3.6
E-055	1-d-old M MPAL	KMT2Ar t(11;14;19)	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: N Other: N/A	2	Y	Y	B-cell: CD19 T-cell: N/A Myeloid: CD33 Other: CD45, HLA-DR, CD38, CD133, CD9, CD40	HD ARA-C/asparaginase → no CR Hydroxyurea, steroids, then menin inhibitor (SNDX-5613) → CR	N	Alive with disease	4.8
E-082	17.1-yo M B-ALL	Hypodiploid	Blinatumomab: Y∗ Inotuzumab: N CAR: N HSCT: Y Other: N/A	8.0	UNK	N	B-cell: CD10, CD20, CD79a T-cell: N/A Myeloid: CD33 Other: TdT, CD45, CD34, HLA-DR	VCR, asparaginase, dexamethasone → no CR VP16, ARA-C, asparaginase, mercaptopurine → no CR Inotuzumab → CR	N	Died from disease	6
E-091	11-d-old F B-ALL	KMT2Ar t(4;11)	Blinatumomab: N Inotuzumab: N CAR: Y∗ HSCT: N Other: N/A	2.4	Y	UNK	B-cell: CD19 T-cell: CD7 Myeloid: CD15, CD64 Other: CD9, CD38, CD34, CD58, HLA-DR	Venetoclax, azacytidine → no CR	N	Died from disease	1.2

ARA-C, cytarabine; CR, complete remission; DA-EPOCH, dose adjusted etoposide, vincristine, doxorubicin, prednisone, cyclophosphamide; DNX-FLA, fludarabine, cytarabine, liposomal daunorubicin EMA, epithelial membrane antigen F, female; FISH, fluorescence in situ hybridization; f/u, follow-up; GO, gemtuzumab ozogamicin; hAM24, high dose cytarabine, mitoxantrone; ID, identity; LD, lineage drift; M, male; MTX, methotrexate; MUM1, multiple myeloma 1; N, no; N/A, not applicable; Ph, Philadelphia chromosome; PR, partial response; RT, radiation therapy; sCD19low, surface CD19; TdT, terminal deoxynucleotidyl transferase; UNK, unknown; VCR, vincristine; VP16, etoposide; Y, yes; yo, year-old.

∗

Most proximal immunotherapy to LS.

‡

KMT2Ar detected at time of second relapse (before LS).

†

Did retain other molecular mutations.

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