Second Opinion Consultation

Patient information

Patient Name: Lara Doe
Date of birth: 01/02/1960
Date of request: 10/01/2016
Data Source: Her son

Family concerns and questions they would like answered:

“I would like to get an opinion on future course of action. The doctor is giving her some injections to increase neutrophil count but they do not seem to be working. Also, although there are no blasts now, her counts are too low. I would appreciate any help you could provide.”

Summary:

Lara Doe is a 59 year old woman residing in India and who was recently diagnosed with precursor B lymphoblastic leukemia. Her first cycle of induction was complicated with neutropenia and sepsis, thus delaying her treatment. Following that induction, she was noted to have recurrence of blasts in her peripheral blood. She was started on a reduced dose re- induction with recurrence of her neutropenia. Her son who would like to know more about her best treatment options for her moving forward.

History of Present Illness:

Mrs Doe is a 59 year old woman with history of Diabetes Mellitus, history of tonsillectomy who was diagnosed with precursor B-ALL on 01/15/2016 after she presented to the hospital. The reason for her presentation is not readily available to us but upon CBC analysis, her peripheral blood results upon presentation were : WBC of 68,000, Hb 10.3 ,Platelet count 38,000.

06/15/2016: She underwent a bone marrow biopsy. The cytogenetics and flow cytometry results are as follows:

Flow cytometry: CD 45 +, CD 34 +, TdT +, CD 117 -, HLA-DR +, CD 10 and CD 19 Co- expression +, CD 20 – , CD 22 cyto +, CD 79a +, IgM – , CD 13 +, CD33 +, MPO –

Impression: overall flow cytometry findings are consistent with precursor B lymphoblastic leukemia/lymphoma (CD10 + ) with aberrant expression of myeloid marker CD 13. Correlation with clinical features, peripheral blood findings, bone marrow morphology and cytogenetic/ molecular studies are essential.

Karyotype : Metaphases counted 20, Metaphases analyzed 20, Metaphases karyotyped 02, Metaphases photographed 02. Karyotype: 45, XX, -7, t (9,15) (q34;q11.2) [20]

Interpretation: All 20 metaphases analyzes are abnormal and show monosomy of chromosome 7 along with unusual t(9;15). Monosomy 7 is associated with acute myeloid leukemia and prognostic implication of t(9;15) cannot be commented upon. Correlation of chromosomal studies with clinical and hematological findings is recommended

06/18/2016: She was started on a modified CALGB chemotherapy regimen with a planned induction consisting of :

Prednisolone Vincristine Daunorubicin L-asparaginase IT

She did not receive cyclophosphamide on day 1, and the mentioned Daunorubicin appears to differ from the routine regimen given from Days 1-3.

Course of treatment: Her induction was complicated with several episodes of neutropenia and sepsis, resulting in a prolonged course of treatment and the need to delay the treatment, which was completed 08/09/2016. Regarding her CNS disease, she received a total of 3 doses of intrathecal therapy over the course of the first induction. Below is what she received:

Prednisolone
20 mg once daily Vincristine Daunorubicin

20 mg twice daily 06/17 -07/15. 07/16- 08/09

2 mg 6/24, 7/10, 7/25, 8/1
40 mg 6/24, 7/10, 7/25, 8/5

30mg PO twice daily 2mg iv

Days 1-d28
Days 1, 8, 15, 29

Days 1, 8, 15, 29
8 doses from Day 12 at interval of 3 days

30mg/m2
10,000
3 times during induction planned on Days 1,12,35

L-asparaginase 10,000 mg 6/28, 7/19, 7/23, 7/25, 7/29, 8/3, 8/6, 8/9 Intrathecal MTX 6/30, 7/15, 7/28

06/25: Lumbar puncture: Positive for blasts

08/10/2016: Last day of course 1 of induction. Received L-asparaginase

08/19/2016: Peripheral blood: positive for 24% blasts.

08/25/2016: Planned for re-induction with the following regiment with the goal to repeat bone marrow in 2 weeks (09/07):

Prednisolone x 7 days Vincristine x 2 doses

Daunorubicin

Treatment received so far: Prednisolone

x 1 dose

30 mg twice daily
08/24, 08/31

Vincristine Daunorubicin Intrathecal MTX

2 mg

40 mg

8/26 08/27, 08/30

08/30/2016: CBC: WBC 2.2 k, Neut 30%, Hb 8.9, plts 85k

09/03/2016: She is receiving filgrastim but remains neutropenic (WBC 1.4 k, Neut 2%, Hb 8.4, plts 43k)

09/10/2016: CBC: Blasts: 24%

08/24- 08/31.

Past medical history:

Diabetes Mellitus

Past surgical history:

Tonsillectomy

Allergies:

No known drug allergy

Performance status:

Limited ability and spends more than 50% in bed. Current PS is 4. Pre-treatment PS: 0 (Active lifestyle)

Social history:

Alcohol use: Does not drink alcohol Tobacco use: Does not smoke

Review of systems:

Limited records to fully evaluate her systems

Assessment and Plan:

1- Precursor B acute lymphoblastic leukemia:

Mrs Doe was diagnosed with precursor B cell ALL. Acute lymphoblastic leukemia, called “ALL,” is a type of blood cancer. ALL is fast-growing and needs to be treated quickly. Blood is made up of different types of cells. These cells are made in the middle of your bones, in a part called the bone marrow.

When people have ALL, their bone marrow makes abnormal blood cells instead of normal blood cells. These abnormal blood cells grow out of control, get into the blood, and travel around the body. Sometimes, these cells collect in certain parts of the body.

When the bone marrow makes abnormal blood cells, it does not make the normal blood cells a person’s body needs.

2-CNS disease

She has CNS disease for which she has received 3 doses of intrathecal chemotherapy during her first induction and two doses during the second induction. Prophylactic radiation has been briefly discussed with her but her course of treatment complicated by neutropenic infections has not allowed for initiation of CNS radiation.

3-Chemotherapy induced neutropenia and infections:

The occurrence of infections has significantly delayed the first course of induction. Despite being on G-CSF injections during the second cycle of induction

4-Decreased Performance status:

Her pre-treatment performance status was 0 but her activity decreased following her diagnosis and treatment to a current PS of 3. Because her performance status is related to treatment, this should not be the deciding factor in her receiving further treatment .

5-Recommendations:

She has failed two induction therapies and at this point, proceeding to an allogeneic stem cell transplant (transferring the stem cells from a healthy person (the donor) to your body after high- intensity chemotherapy or radiation.

There are a number of different salvage options at this stage: 1- FLAG,
2- high-dose cytarabine,
3- cytarabine-mitoxantrone.

There is no clear reason to prefer one over another. However, unless she can get an allogeneic transplant the likelihood of a durable benefit is unfortunately small. In the US she would be considered for blinatumomab either when she has minimal residual disease (not the case now) or as a bridge to transplant.