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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