TRAINING and EDUCATION
You Make the Call
Each month in “You Make the Call,” we pick a challenging clinical question submitted through the Consult a Colleague program
and post the expert’s response, but we also want to know what you would do. Send in your response to next month’s clinical
dilemma and see how your answer matches up to the expert’s in the next print issue.
This month, Wendy Stock, MD, discusses best options for an older patient with Philadelphia chromosome (Ph)–positive B-cell
acute lymphocytic leukemia (ALL).
Clinical Dilemma:
I have a 66-year-old female patient recently diagnosed with Ph-positive B-cell ALL. Conventional cytogenetics showed
hyperdiploid karyotype plus FISH/PCR positive for BCR-ABL. After four cycles of hyper-CVAD (cyclophosphamide,
vincristine, doxorubicin, dexamethasone) plus dasatinib, PCR is negative. Bone marrow aspirate is also negative for
ALL. Should she be considered for allogeneic hematopoietic cell transplantation (alloHCT)?
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Wendy Stock, MD
Professor of Medicine
Director, Leukemia Program
University of Chicago
• Anemias
I believe that there is potential equipoise
about the optimal post-remission treat-
ment approach in 2019. While the general
recommendation from most studies in
Ph-positive ALL is to perform an alloHCT
in first complete remission (CR1) if the
patient is a candidate, there are pros and
cons to this approach.
A landmark analysis performed at 175
days from the time of CR/CRi demonstrated
a statistically superior advantage for both
relapse-free survival (RFS) and overall survival
(OS) for patients who received a transplant in CR1
after an induction with hyper-CVAD plus dasatinib,
much like the patient in question. 1 However, the maxi-
mum age of patients enrolled in this study was 60 years.
Furthermore, there were no data on the impact of min-
imal residual disease (MRD) on RFS and OS in patients
who did/did not receive transplant in this study. Interest-
ingly, MD Anderson also published data on the impact
of MRD status after hyper-CVAD plus dasatinib. A 2016
study demonstrated that patients with Ph-positive ALL
treated with hyper-CVAD plus a tyrosine kinase inhibitor
(TKI) achieved a complete molecular response at three
months (which appears to be the case in your patient),
and their survival was excellent, even without alloHCT. 2
My approach for older adults with Ph-positive ALL
involves a much less intensive induction/consolidation
with TKI-based therapy with or without transplant
depending on response, patient suitability, and desire for
transplant – as per the CALGB 10701 trial. 3 However,
additional data are beginning to affect my approach to the
older adult with Ph-positive ALL in CR1. Both blinatum-
omab and inotuzumab ozogamicin have been approved
for relapsed Ph-positive ALL, and blinatumomab has
been approved to treat MRD-positive Ph-positive ALL
and can result in long-term disease-free survival even
without transplant. 4,5 The use of the third-generation TKI
ponatinib also may be even more effective in achievement
of complete molecular remissions and appears to result
in improved event-free survival compared with histor-
ical controls in a single institution study, also without
transplantation. 6 There are still no studies that carefully
examine the optimal duration of TKI therapy with or
without transplant, although prolonged therapy appears
beneficial, even after transplant. Prospective cooperative
group or multicenter studies will be useful to test some of
ASHClinicalNews.org
• Hematopoietic cell
transplantation
• Hemoglobinopathies
• Hemostasis/thrombosis
• Lymphomas
• Lymphoproliferative disorders
• Leukemias
• Multiple myeloma & Waldenström
macroglobulinemia
• Myeloproliferative neoplasms
• Myelodysplastic syndromes
• Thrombocytopenias
these exciting approaches to achieve MRD-negativity in
Ph-positive ALL, which can improve quality and duration
of life for our patients.
REFERENCES
1. Ravandi F, Othus M, O’Brien SM, et al. US Intergroup Study of chemotherapy plus dasatinib
and allogeneic stem cell transplant in Philadelphia chromosome positive ALL. Blood Adv.
2016;1:250-9.
2. Short NJ, Jabbour E, Sasaki K, et al. Impact of complete molecular response on survival in
patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood.
2016;128:504-7.
3. Wieduwilt MJ, Yin J, Wetzler M, et al. A phase II study of dasatinib and dexamethasone as
primary therapy followed by transplantation for adults with newly diagnosed Ph/BCR-ABL1-
positive acute lymphoblastic leukemia (Ph+ ALL): final results of Alliance/CALGB Study
10701. Abstract #309. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San
Diego, CA.
4. Kantarjian H, Stein A, Gokbuget N, et al. Blinatumomab versus chemotherapy for advanced
acute lymphoblastic leukemia. N Engl J Med. 2017;376:836-47.
5. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard
therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375:740-53.
6. Jabbour E, Short NJ, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-
line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic
leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol.
2018;5:e618-27.
Next Month’s Clinical Dilemma:
Another clinician ordered a JAK2 test on a patient for
unclear reasons. It was positive. The patient’s counts are
normal, and there are no thromboembolic events. What
is the significance of this? Should anything be done?
How would you respond? Email us at
[email protected]. ●
Assigned volunteers (“colleagues”) will
respond to inquiries within two business
days (either by email or phone).
Have a puzzling clinical dilemma?
Submit a question, and read more
about Consult a Colleague volunteers at
hematology.org/Clinicians/Consult.aspx
or scan the QR code.
* If you have a request related to a
hematologic disorder not listed here,
please email your recommendation to
[email protected] so it can be
considered for addition in the future.
DISCLAIMER: ASH does not recommend
or endorse any specific tests, physicians,
products, procedures, or opinions, and
disclaims any representation, warranty, or
guaranty as to the same. Reliance on any
information provided in this article is solely
at your own risk.
ASH Clinical News
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