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Table 2 Early 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

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

Status/Relapse Treatment

 

7

61/INT-1

RARS /46,XX,del(12)(p11.2p13) [7]/46,XX [13]

RARS/46,XX,del(12)(p11.2p13) [3]/46,XX [17]

No intervening marrows pre-transplant

Indeterminate /6 /Neg by FISH

MDS with dyerythropoiesis and numerous ring sideroblasts, no increase in blasts c /88 /46,XX[49]//46,XY[1]

  

Deceased of invasive aspergillus lung infection with persistent MDS/ reduction in immunosuppression then DLI for subsequent RAEB-1

Some similarities between clones

Daysb

 

−699

−15

 

23

100

  

237/137 (post-relapse)

 

27

69/Unknown

RCMD-RS

RCMD-RS/45,XY,-7,del(20q)(q11.2q13.1) [3]

No intervening marrows pre-transplant

Indeterminate /30.6 / monosomy 7 by FISH (8% interphase cells)

Negative /0 /monosomy 7 by FISH (2.75%, slightly above normal control range)

Negative /0 /not performed

MDS with dysmegakaryopoiesis, numerous ring sideroblasts, no increase in blasts /12.6 /45,XY,-7,del(20q)(q11.2q13.3)[3]/46,XY[12]

Unknown/ Unknown

Same abnormal clone

Days

 

−111

−31

 

22

60

98

155

  

32

62/INT-1

RAEB-1

RAEB-2/clone with trisomy 8

Hypercellular marrow withno increase in blasts; 3.25% by FISH with extra chromosome 8

Indeterminate /6.1 /Neg by FISH

Indeterminate /11.8 /Neg by FISH and karyotype

AML /41.8 /46,XX,t(2;3)(q23;q26–27)[4]/46,XX[14]

 

Unknown/ Unknown

Different abnormal clone

Days

 

−376

−141

−29

33

63

98

   

34

49/HIGH

RAEB-1 /complex karyotype including deletion of 5q

Same specimen as original MDS diagnosis

Normocellular marrow with no increase in blasts/cytogenetics not performed

Negative /57.4 /Neg by FISH

Negative /29.6 /loss of chromosome 5 by FISH (6.75% interphase cells) and complex karyotype

MDS with dysgranulopoiesis, borderline increased marrow blasts, and rare circulating blasts / 20.3/FISH: 19.5% had a signal pattern indicative of loss of both 5p15.2 and q31

 

Unknown/ Unknown

Some similarities between clones

Days

 

−200

 

−25

21

36

65

   

58

67/LOW

MDS with isolated del(5q) /46,XY,del(5)(q13q33) [18]/46,XY [2]

RAEB-2/46,XY,del(5)(q22q33) [18]/46,XY [2]

No intervening marrows pre-transplant

Indeterminate /0 /Neg by FISH

Indeterminate /3 /Neg by FISH

RAEB-1 /38 /46,XY,del(5)(q22q35)[11*]/46,XY[7]/46,XX[2]

 

Unknown/ Unknown

Same abnormal clone

Days

 

−458

−25

 

21

98

137

   

63

68/INT-2

RCMD-RS /45~46,XY,add(4)(q31),del(5)(q15q33),del(7)(q22q34),+8,del(11)(q14q23),add(12)(p11.2),dic(14;15)P(11.2;p11.2),add(17)(p11.2),-18,01mar[cp18]/46,XY [2]

RAEB-2/44–46,XY,-3,del(4)(q31q35),del(5)(q15q33),del(7)(q22q36),+8,del(11)(q21q23),add(12)(p11.2),dic(14;15)(p11.2;p11.2),-17,-18,+2mar[cp5]

Normocellular marrow with no increase in blasts/ Negative by FISH

Negative /2.9 /Neg by FISH

RAEB-2 /91.8 /FISH: 83% had a signal pattern consistent with deletion of the long arm of one chromosome 5

  

Unknown/ azacitidine

Some similarities between clones

Days

 

−298

−126

−15

21

90

  

129/39 (post-relapse)

 

78

69/LOW

RARS-T /46,XY,dup(1)(q21q43) [14]/46,XY,der(15)t(1;15)(q12;p11.2) [3]/46,XY [3]

Same specimen as original MDS diagnosis d

No intervening marrows pre-transplant

Indeterminate/0 /Neg by FISH

Negative/7 /Neg by FISH

Abnormal with 5% ring sideroblasts /14 /46,XY,dup(1)(q21q43)[2]/46,XY,der(15)t(1;15)(q12;p11.2)[1*]/46,XY[17]

 

Deceased with steroid refractory late acute GVHD/No intervention

Same abnormal clone

Days

 

−21

  

23

100

174

 

232/58 (post-relapse)

 

79

70/INT-2

RAEB-1 /43–44, XX, −5, −7, −19, −22, +12mar [3]/4245, sl, −18, +14[11]/46,XX [6]

Same specimen as original MDS diagnosis

Persistent MDS with 3% marrow blasts/44,XX,-5,-7,-18,-19,-22,+3mar [2]/46,XX [19]

Negative/ not performed /Neg by FISH

Suspicious for myeloid neoplasm with slight trilineage dyspoiesis and 4% to 5% blasts /23 /44,XX,-5,-7,-19,-22,+mar1,+mar2[3]/43,idem,-18[2]//46,XY[15]

  

Alive currently undergoing treatment for relapse (as AML) that occurred 2 years after DLI/ immunosuppression withdrawal

Same abnormal clone

Days

 

−70

 

−28

20

90

  

625/535 (post-relapse)

 

81

71/INT-1

RAEB-1

RAEB-1/Normal karyotype

No evidence of residual disease/cytogenetics not performed

Negativee /38 /normal karyotype

RAEB-1 / 26/46,XX[19]

  

Deceased with persistent disease/withdrawal of immunosuppression then ALT-803 trial

No clonal abnormality pre-transplant disease and relapse

Days

 

−735

−165

−38

21

98

  

465/367 (post-relapse)

 

82f

34/INT-1

RCMD /46,XY,add(6)(?p21.2) [18]/46,XY [2]

RAEB-1/46,XY,add(6)(p21.1) [20]

No intervening marrows pre-transplant

Indeterminate/0 /normal karyotype

Indeterminate /0 /normal karyotype

Indeterminate /1 /not performed

AML /66 /46,XY,add(6)(p21.1)[4]/46,idem,t(9;14)(q34;q24)[14]/46,X,t(Y;1)(p11.3;q21),del(4)(q11), der(13)t(4;13)(q11;p13),add(6)[2]

Deceased with persistent disease/ 7 + 3 induction, ALT-803, GCLACchemotherapy, azacitidine, DLI

Clonal evolution

Days

 

−230

−35

 

21

62

99

139

374/235 (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, RARS Refractory anemia with ring sideroblasts, RCMD refractory cytopenias with multilineage dysplasia, RCMD-RS refractory cytopenias with multilineage dysplasia and ring sideroblasts, RAEB refractory anemia with excess blasts, AML acute myeloid leukemia, 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
  3. aEngraftment is reported as % recipient
  4. bDays are relative to transplant date unless otherwise noted
  5. cBone marrow biopsy 2 months after showed RAEB-1
  6. dPatient carries diagnosis of RARS-T since 2007, reason for transplant is clonal progression and development of transfusion requirements
  7. eCase 81 was called positive on study review due to increased blasts
  8. f Received myeloablative chemotherapy pre-transplant