Raymond E Felgar MD PhD University of Pittsburgh Pittsburgh PA 45yearold man with recent history of shingles night sweats and gum swelling Hematologic testing showed the following WBC 69300 Hgb 235 Platelets 114000 ID: 589232
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Case 251: Clinical InformationRaymond E Felgar, MD, PhDUniversity of Pittsburgh, Pittsburgh, PA
45-year-old man with recent history of shingles, night sweats and gum swelling.
Hematologic testing showed the following:
WBC 69,300 / Hgb 23.5 / Platelets = 114,000
Leukocyte Differential 55.5% Blasts.
Bone marrow examination performed.Slide2
Case 251: Blood Smear FindingsSlide3
Bone Marrow Aspirate DifferentialSlide4
Bone Marrow Aspirate, Wright-Giemsa,
1,000xSlide5
Biopsy, H&E, 1,000xSlide6
Flow CytometrySlide7
Case 251: Flow Summary
Two prominent cell populations:
1) 41% CD34+ myeloblasts marking as follows:
CD34+, dim CD45+, CD13/33+, CD14-, CD36 (partial+), CD64+, CD117+, CD15 (partial+), HLA-DR+, CD33+, CD56-, CD13+,
CD11b (partial+), partial MPO+.
2) 37% CD14+ monocytes marking as follows:
CD34-, bright CD45+, CD13/33+, CD14+, CD36+, CD64+, CD117-, CD15+, HLA-DR+, bright CD33+, CD56-, CD13 (partial+), CD11b+, probable partial MPO+.
Slide8
Myeloperoxidase CytochemistrySlide9
Double Esterase: Black = a-naphthyl acetate esterase Red = Chloroacetate esteraseSlide10
Cytogenetics: 46, XY, t(6:11)(q27;q23)Slide11
FISH: Cell with One Intact MLL (Red Arrow), One Rearranged (Split Signal, Yellow Arrows) Slide12
Case 251: Other Data FLT3 ITD Positive, D835 Negative
NPM1 UnmutatedSlide13
Case 251: Diagnosis
Submitted Diagnosis:
Acute myeloid leukemia with t(6;11)(
q27;q23
) and MLL gene rearrangement. Consensus Diagnosis:Acute myeloid leukemia with t(6;11)(q27;q23
).Slide14
Case 251: Clinical CourseInduction chemotherapy with achieval of remission status.
In Jan 2013, received matched unrelated stem cell transplant.
Mild graft vs. host disease, now apparently resolved.
Most recent marrow (April 2013) indicated both morphologic and cytogenetic remission (FISH negative for MLL rearrangement.) Slide15
Case 251: DiscussionShould we include AML with t(6;11)(
q27;q23
) amongst cases with defined translocations?
Should t(6;11) be considered a leukemia defining translocation, regardless of blast percentage?Slide16
Case 251: DiscussionSUMMARY POINTS
6q27
gene partner:
MLLT4
RAS pathway activationWorse prognosticallyAssociated with AML-M4 or M5 morphologySlide17
Case 251: AML with t(6;11)(q27;q23): Clinical and Laboratory Studies Supporting Recognition as Specific Disease
Martineau M et al. Leukemia 1998;12:788-91.
Blum W et al. Cancer 2004;101:1420-7.
Grimwade D et al. Blood 2010;116:354-365.Slide18
Case 251: AML with t(6;11)(q27;q23): Clinical and Laboratory Studies
Martineau M et al. Leukemia 1998;12:788-91.
30 cases (5.5% of cases studies as part of an EU Concerted Action Workshop on
11q23
in haematological malignancy).22 of 30 (73%) had M4, M4/5, or M5 morphology
3
M1
, 2
M2
, 3 ALL (2 B, one T lineage)
Median survival = 12 months, with median
event free survival of 7.8 month.
Slide19
Case 251: AML with t(6;11)(q27;q23): Clinical and Laboratory Studies
Blum W et al. Cancer 2004;101:1420-7.
CALGB
study of 2667 AML cytogenetic database
16 patients (0.6% of database) with additional review of 33 adult cases.81% had M4 or M5 morphologyFrequent gingival involvement (31% cases)CR in 69%, CR duration (median, 9 mos
),
2 Year OS of 13%, literature 15%.
2 long term survivors, both after allogeneic hematopoietic stem cell transplant.Slide20
Case 251: AML with t(6;11)(q27;q23): Clinical and Laboratory Studies
Grimwade
D et al. Blood 2010;116:354-365.
Outcome data of 5876 patients in UK Medical Research Council Trials (ages 16-59
yrs).Focussed on outcomes in less common abnormalities, each with incidence <2%.Identified t(6;11) as poor prognostic groupSurvival curve (grouped with “other 11q23”) slightly better than AML with MDS related cytogenetic changes (i.e. cases with -7, del(7q
), -5, del(
5q
), or other MDS-related).Slide21
Conclusions?
AML with t(6;11)(q27;q23) in poor prognostic group.
Although not common, probably should be recognized as separate disease.
Should we define cases with <20% blasts as AML?
Not sure, but probably? (Limited data regarding translocation behavior in low blast count setting.)Slide22