Table 3.
Late Relapse Cases
| Study No | Age at transplant/IPSS score | Original MDS Diagnosis | Pre-transplant MDS Diagnosis | Immediate pre-transplant Marrow Biopsy (following cytoreductive therapy) | Post-transplant Assessment 1 | Post-transplant Assessment 2 | Post-transplant Assessment 3 | Post-transplant Assessment 4 | Post-transplant Assessment 5 | Post-transplant Assessment 6 | Post-transplant Assessment 7 | Post-transplant Assessment 8 | Post-transplant Assessment 9 | Follow-up | Cytogenetics Comparison |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diagnosis/CG | Diagnosis/CG | Diagnosis/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Morphologic Conclusion/Engraftmenta/CG | Status/Relapse Treatment | |||
| 10b,c | 51 /INT-2 | RCMD/45,XX,-5,add(7)(q11.2) [8]/41–43,XX,-5,add(7)(q11.2),-12,-16,-18,-20[cp4]/46,XX [9] | RCMD/45,XX,-5,add(7)(q11.2) [4]/42,idem,-12,-16, −20[6]/49,XX [10] | No intervening marrows pre-transplant | Negative /0 /Neg by karyotype | AML /47.6 /Abn by FISH. 36% with loss of the long arm of one chromosome 5 and 41.5% had a signal pattern consistent with loss of the long arm of chromosome 7 | Deceased of sepsis with persistent disease/ 7 + 3 induction, LYF73636, Haplo NK | Some similarities between clones | |||||||
| Daysd | −129 | −17 | 95 | 1477 | 1599 /122 (post-relapse) | ||||||||||
| 17 | 50 /INT-1 | RCMD/ 46,XX,+1,der(1;7)(q10:p10) [15]/46,XX [5] | RCMD/46,XX,+1,der(1;7)(q10;p10) [5]/46,XX,-7,+21[11]/46,XX [4] | No intervening marrows pre-transplant | Negative /0 /Neg by FISH | Negative /0 /not performed | Negative /0 /not performed | Negative /0 /not performed | Negative /0 /Neg by FISH | Negative /0 /Neg by FISH | RAEB-2 /15 /45,XX,-7[4]//46,XY[108] | Deceased of GVHD, stroke, and multiorgan dysfunction with persistent disease/ Chemo + DLI | Some similarities between clones | ||
| Days | −849 | −17 | 21 | 61 | 98 | 182 | 367 | 733 | 2449 | 2604 /155 (post-relapse) | |||||
| 33 | 46 /INT-2 | RAEB-2/46,XX [20] | Same specimen as original MDS diagnosis | Normocellular marrow with no dysplasia and no increase in blasts/normal karyotype | Negative /37.5 /not performed | Negative /0 /not performed | Negative /0 /not performed | Indeterminate e /0 /46,XX,t(6;12)(p22;p13) [3]/46,XX [1]//46,XX[16] | AML /26.1 /46,XX,t(6;12)(p22;p13)[9]//46,XX[11] | Alive in on-going remission/ Induction Chemotherapy then Haplo NK with transplant | Different abnormal clone | ||||
| Days | −90 | −17 | 21 | 101 | 182 | 364 | 410 | 2302 /1892 (post-relapse) | |||||||
| 39 | 59 /INT-1 | RAEB-1/46,XY,add(11)(q13) | RAEB-1/46,XY,der(11)t(3;11)(q13.2;q13) [15]/46,XY [5] | No intervening marrows pre-transplant | Negative /72.5 /derivative 11 in 2 of 6 male (recipient) metaphases | Negative /70.7 derivative 11 in 7 of 12 male metaphases | Negative /12.4 /derivative 11 in 2 of 2 male metaphases | Negative /13.2 /derivative 11 in 4 of 4 male metaphases and 2 with additional t(1;7;13)(p31;q22;q13) | Negative /42.7 /deritivative 11 in 9 of 9 male metaphases with and 2 with additional t(1;7;13) | RAEB-1 /68.3 /chi 46,XY,der(11)t(3;11)(q13.2;q13)[14]/46,idem,t(1;7;13)(p31;q22;q13)[3]/46,XX[3] | Unknown/ Unknown | Clonal evolution | |||
| Days | −244 | −15 | 21 | 66 | 170 | 352 | 546 | 658 | |||||||
| 61 | 58 /INT-2 | RAEB-2/Normal karyotype | Same specimen as original MDS diagnosis | Slightly hypocellular marrow with no dysplasia and no increase in blasts/normal karyotype | Negative /41 /not performed | Negative /0 /not performed | Indeterminate /0 /Neg by karyotype | Negative /0 /Neg by karyotype | RAEB-2 /48 /46,XY[15]//46,XY[5] chimerism based on G-band polymorphisms | Deceased of metastatic urothelial carcinoma with MDS /azacitidine | No clonal abnormality pre-transplant disease and relapse | ||||
| Days | −106 | −14 | 20 | 101 | 178 | 392 | 722 | 840 /118 (post-relapse) | |||||||
| 66 | 61 /unknown | RAEB-2/46,X,idic(X)(q13)[17]46,XX [3] | RAEB-2/46,X,del(X)(q22q26) [2]/46,X,t(X;10;3)(q26;q21;q12) [2]/46,XX with nonclonal abnormalities [2]/46,XX [4] | Hypocellular marrow with slight dysgranulopoiesis and 4% blasts/46,X,idic(X)(a13) [16]/46,XX [4] | Negative /5.1 /Neg by karyotype | Indeterminate e /0 /Negative by karyotype | AML /60.9 /45,XX,-7[2]/46,idem,+21[8]/46,XX[10] | Deceased of infection and persistent disease/ withdrawal of immunosuppression | Different abnormal clone | ||||||
| Days | −243 | −107 | −30 | 21 | 152 | 364 | 404 /40 (post-relapse) | ||||||||
| 67 | 60 /High | MDS-U/unknown | MDS-U with <5% marrow blasts/47,XY,+8,inv.(12)(p13q13) [7]/46,XY [13] | No intervening marrows pre-transplant | Negative /4.8 /Neg by karyotype | Negative /2 /Neg by FISH | Indeterminate /0 /Neg by karyotype | Negative /0 /not performed | Negative /4.4 /Neg by karyotype | RAEB-1 /91.8 /47,XY,+8,t(8;17)(q24.1;p13),inv.(12)(p13q13)[20] | Deceased/ Haplo NK with IL-2 and Transplant | Clonal evolution | |||
| Days | −84 | −15 | 7 | 57 | 88 | 172 | 252 | 310 | 632 /322 (post-relapse) | ||||||
| 74b | 59 /INT-2 | RAEB-1/45,XY,-7[19]/46,XY [1] | Same specimen as original MDS diagnosis | Normocellular marrow with no increase in blasts/Negative by FISH | Negative /0 /Neg by karyotype | Negative /3 /Neg by FISH | Negative /0 /Neg by FISH | Negative /0 /Neg by FISH | Negative /0 /Neg by FISH and karyotype | AML /not performed /45,XY,-7[14]/46,XY[6] | Deceased/ Hospice | Same abnormal clone | |||
| Days | −161 | −27 | 20 | 99 | 127 | 192 | 358 | 583 | 583 | ||||||
| 75b | 58/ INT-2 | T-MDS/normal karyotype | T-MDS with >10% marrow blasts/normal karyotype | Slightly hypocellular marrow with minimal dysplasia and no increase in blasts/unknown | Negative /0 /Not performed | Negative /0 /not performed | Early relapsed myeloid neoplasm with slight trilineage dyspoiesis, borderline increased marrow blasts, and rare circulating blasts f /9 /46,XX[20] | Deceased in hospice with progression to AML/ Immunosuppression withdrawal | No clonal abnormality pre-transplant disease and relapse | ||||||
| Days | −205 | −130 | −30 | 21 | 96 | 181 | 298 /117 (post-relapse) | ||||||||
| 76 | 46 /INT-1 | RAEB-2/46,XY,inv.(3)(q21q26.6) [6]/46,sl,+14,i(14)(q10) [3]/46,XY [11] | Same specimen as original MDS diagnosis | Slightly hypocellular marrow with mild dysplasia and no increase in blasts/normal karyotype | Indeterminate /6 /46,XY,inv.(3)(q21q26.2) [1]/46,XY [18].nuc ish(EVI1x2)(5’EVI1 sep 3’EVI1x1)[4/800] | Negative /6 /Neg by FISH and karyotype | Negative /2 /Negative by FISH and normal karyotype | Negative /7 /Negative by FISH and normal karyotype | Negative /0 /Neg by FISH | Negative (graft failure) /8 /Neg by FISH | Negative /8 /Neg by FISH | Negative /4 /not performed | Relapsed MDS with dysplastic granulocytes and megakaryocytes, 4% to 7% blasts, and rare circulating blasts /68 /46,XY,inv.(3)(q21q26.2)[9]/46,XY[11] | Alive in complete remission with GVHD/ Stem cell boost for graft failure (after 328 day marrow); second allogeneic sibling transplant for relapse | Same abnormal clone |
| Days | −102 | −34 | 20 | 65 | 132 | 206 | 311 | 328 | 336 | 388 | 462 | 1001 /539 (post-relapse) | |||
| 80c | 55 /INT-1 | MDS associated with myelofibrosis/46,XX, t(3;8)(q26.2;q24.1) [17]/46,XX [3] | MDS associated with myelofibrosis g/46,XX,t(3;8)(q26.2;q24.1) [3]/46,XX [17] | Hypocellular marrow with slight dysgranulopoiesis and borderline increased blasts/not performed | Negative /0 /Neg by FISH | Negative /0 /Neg by FISH | Negative /0 /Neg by FISH | RAEB-2 /45 /46,XX,t(3;8)(q26.2;q24.1),del(5)(q11.2),del(11)(p11.2p15),der(12)t(5;12)(q11.2;p11.2)[cp7]/46,XX[12] | Deceased of disease/ ALT-803 trial | Clonal evolution | |||||
| Days | −375 | −166 | −18 | 21 | 100 | 183 | 370 | 436 /66 (post-relapse) |
RELAPSE MARROWS in BOLD
Abbreviations: IPSS International prognostic scoring system, MDS myelodysplastic syndrome, CG cytogenetics, INT-1 Intermediate-1, INT-2 Intermediate-2, RCMD refractory cytopenias with multilineage dysplasia, RAEB refractory anemia with excess blasts, MDS-U myelodysplastic syndrome, unclassifiable, AML acute myeloid leukemia, T-MDS therapy related myelodysplastic syndrome, FISH fluorescence in-situ hybridization, DLI donor lymphocyte infusion, GCLAC G-CSF priming, clorarabine, and high dose cytarabine, ALT-803 trial IL-15 Superagonist Clinical Trial, GVHD graft versus host disease, LYF73636 clinical trial
a Engraftment is reported as % recipient
b Patient has a history of cytotoxic chemotherapy
c Received myeloablative transplant
d Days are relative to transplant date unless otherwise noted
e Case 33 was called positive on study review due to identification of rare blasts with Auer rods; Case 66 was called positive on study review due to trilineage dysplasia including abnormal lobation of granuloccytes, small and hypolobated megakaryocytes, and ring sideroblasts
f Progressed to AML 2 months after with only withdrawal of immunosuppression in intervening time
g Institutional review reports as MDS associated with myelofibrosis versus RAEB-1