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Table 3 Late Relapse Cases

From: Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach

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)  
  1. RELAPSE MARROWS in BOLD
  2. 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
  3. a Engraftment is reported as % recipient
  4. b Patient has a history of cytotoxic chemotherapy
  5. c Received myeloablative transplant
  6. d Days are relative to transplant date unless otherwise noted
  7. 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
  8. f Progressed to AML 2 months after with only withdrawal of immunosuppression in intervening time
  9. g Institutional review reports as MDS associated with myelofibrosis versus RAEB-1
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