Heme Aml

Front 1

AML Genetics

Back 1

Other poor risk cytogenetic groups:

Deletion 7 and deletion 5

Complex ≥ 3 abnormalities

Inversion (3)

Trisomy 8

t(6;9)

t(11;19)

**t(9;22) is adverse group in SWOG. +8 Intermediate in SWOG

Intermediate risk cytogenetic groups:

Normal cytogenetics

Good risk cytogenetic groups:

Inversion (16), t(8;21), t(15;17)

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Gvhd and asplenia

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Streptococcus Pneumoniae.

Chronic GVHD can lead to hyposplenia/compromised splenic macrophages which can cause predilection to infections with encapsulated organisms including E. Coli, Haemophilus influenzae, Klebsiella pneumoniae, Neisseria meningitidis, Salmonella typhi, and Streptococcus pneumoniae.

In addition, hypogammaglobulinemia and the compromised ability to react to polysaccharide antigens is often seen in patients who have received allografts and have chronic GVHD.

These patients should be considered for lifelong penicillin prophylaxis.

Kulkarni S et al. Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants. Blood 2000; 95(12): 3683-3686

Front 3

Aml normal cyto mollecular

Back 3

Correct

NPM1: Found in about 30% of AML and up to 60% in cytogenetically normal AML. It confers a favorable OS. If the cytogenetics are normal, having an NPM mutation makes it favorable subgroup

CEBPA: If a biallelic mutation is seen, there is a higher CR and favorable OS.

KIT: Mutations are associated with an inferior outcome.

FLT3-ITD: 20% of AML. It carries an inferior outcome.

FLT-TKD: Has a more controversial significance.

Marcucci Get al. Molecular genetics of adult acute myeloid leukemia: prognostic and

therapeutic implications. J Clin Oncol 2011;29(5):475-86

Front 4

Aml when to do lp

Back 4

Incorrect

Right answer is A) Lumbar puncture.

If you see M4/M5 or a White blood count over 100,000 cells/mcL, consider a lumbar puncture (LP) in remission. These patients are at higher risk of having CNS disease.

Also, if you see biphenotypic morphology, consider LP in remission.

http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf

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Differentiation syndrome

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Differentiation syndrome can occur when patients with APML undergo induction therapy with ATRA and/or Arsenic trioxide.

Fever, elevation of Wbc, dyspnea, decreased oxygen saturation, effusions (pleural and pericardial) and weight gain can occur with this syndrome. Patients can also develop hypotension and ARF. CXR will reveal diffuse interstitial pulmonary infiltrates.

Promyelocytes have granules. When the promyelocytes differentiate with ATRA- based therapy, the granules can stimulate pulmonary edema and lead to fluid retention.

At the first sign of this, must start Dexamethasone immediately (10 mg PO/IV bid x 3-5 days and then taper). Consider interrupting ATRA if there is progression of the clinical symptoms of the differentiation syndrome.

Montesinos P et al. Differentiation syndrome in patients with acute promyelocytic leukemia

Front 6

Apl atra and arsenic alone

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Correct

A phase III study compared ATRA + Arsenic Trioxide vs. ATRA + Chemotherapy

1) ATRA + Arsenic trioxide group:

--Received both drugs daily until CR was achieved

--Then arsenic trioxide 5 days/week, 4 weeks on/4 weeks off, for atotal of 4 courses and ATRA 2 weeks on/2 weeks off for a total of7 courses. The total duration was 28 weeks

2) Standard treatment arm:

--ATRA + Idarubicin induction therapy

--Followed by consolidation with ATRA + Anthracycline and ATRA andmitoxantrone x 3 cycles

--Followed by ATRA plus low-dose chemotherapy maintenance therapy for 2 yrs

Patients had non-high risk APML (white cell count ≤10×109/L). The 2-year EFS was 97% in ATRA + Arsenic Trioxide vs. 86% in the ATRA-Chemotherapy arm(P<0.001 for noninferiority). OS (98.7% vs. 91.1%; P=0.02) favored ATRA + Arsenic.

Lo-Coco F et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013;369(2):111-21

Front 7

Aml post tx vod

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Correct

VOD occurs in part to injury of the small veins in the liver. If you see ascites, hepatomegaly, elevation of bilirubin less than 3 weeks after a transplant, think of this condition. Severe VOD can lead to multiorgan failure. Ultrasound of the liver can show reversal of portal flow.

Diagnosis of VOD includes have 2 of the following before 20 days s/p transplant:

1) Bilirubin > 2.0 mg/dl

2) Painful hepatomegaly

3) Weight gain (>2% from baseline)

Cyclophosphamide and busulfan (PO > IV) conditioning has been reported to cause VOD. Gemtuzumab Ozogamicin also can cause VOD.

Treatment: Largely supportive care. Defibrotide can be given to treat VOD. Some give Defibrotide 6.25 mg/kg IV qid to prevent VOD in patients with high risk factors (busulfan-containing regimens, prior therapy with gemtuzumab ozogamicin, pre-existing hepatic disease).

Coppell JA et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence,

clinical course, and outcome. Biol Blood Marrow Transplant 2010;16(2):157-68.

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Passenger lymphocyte syndrome

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This is likely passenger lymphocyte syndrome. It can occur several days to up to several weeks after a transplant.

Immune hemolysis can occur s/p a bone marrow or peripheral blood stem cell transplant whenever there is ABO incompatibility between the donor and recipient. However, other blood groups including Lewis and Rh can be involved.

The drop in hemoglobin is due to hemolysis. The B lymphocytes from a donor (often a female) can form anti-A antibodies that can attack the recipient's red blood cell antigens (which carry the A antigen).

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Conditioning regimen allo

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A seminal study published in 2013 showed the superiority of IV Busulfan + Cyclophosphamide over earlier conditioning regimens prior to a stem cell transplant. This regimen had significantly less nonrelapse mortality, a lower rate of relapse at 1 year (or more) post-transplant and a better leukemia-free survival.

Of note, the myeloablative regimen of IV Busulfan and Fludarabine has reduced toxicity but similar survival and nonrelapse mortality to IV Busulfan/Cyclophosphamide. The clinical trial, AAML 1031, is evaluating this former regimen.

Front 10

Apl when to start atra

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Correct

Flow cytometry for patients with APML reveals the following:

HLA-DR-, CD34-, MPO+, CD33+

APML is also characterized by DIC. For this patient, start ATRA immediately. The mortality rate for APML is largely due to the attendant bleeding diathesis. If the diagnosis is incorrect on further bone marrow analysis/molecular testing, one can always stop the ATRA.

Sanz MA et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2009 Feb 26;113(9):1875-91

Front 11

Aml molecular 2

Back 11

Correct

The IDH2 mutation, but not the IDH1 mutation, is associated with a favorable prognosis. Mutations in CEBPA is also associated with a favorable prognosis.

If a patient with AML has a normal karyotype or if a patient with AML has intermediate risk cytogenetics and is FLT3/ITD negative:

1) The presence of a mutation in TET2, MLL-PTD, ASXL1 or PHF6 triages a patient to the unfavorable category

2) Being wild-type for ASXL1, MLL-PTD, PHF6, and TET2 puts a patient in the Intermediate category

Patel JP et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012 Mar 22;366(12):1079-89

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AML - Familial AML - MDS.

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CEBPA - No signs or Symptoms prior

100% Penetrant- 19q13.1

Familial PLT DISORDER1 --> FPD - Autosomal Dominant

- Average 33 yr

Need baseline BMBX

- RUNX 1 Gene

THC2 - AD Mod Thromboctytopenia -

Need Baseline BMBX

ANKRD26