Leukemia Management

Introduction

Leukemia is an umbrella term for a number of cancerous blood cell diseases. The kind of blood
cell that turns cancerous and the rate of progression define the classification of leukemia.
Leukemia is the most common malignancy in children under the age of 15, while it is more
common in people over the age of 55. Fatigue, shortness of breath, fever or night sweats,
bruising or bleeding, discomfort in the bones and joints, and repeated infections are the most
typical symptoms of leukemia. The kind of leukemia you have, your age, your general health,
and whether or not the cancer has spread to other parts of your body all influence the sort of
treatment you will get. Chemotherapy, immunotherapy, targeted therapy, radiation therapy,
hematopoietic cell transplantation (bone marrow transplant), and chimeric antigen receptor
(CAR) T-cell therapy are examples of prevalent therapies (Bernard et al., 2017).

Over-20-year-olds have a 40% chance of surviving another 5 years. For individuals under the
age of 20, the 5-year survival rate is 89%. The average lifespan of a person with ALL has
increased dramatically as a result of recent advancements in therapy. However, a variety of
circumstances, including the patient's age and the biological characteristics of the condition,
influence the likelihood of survival. With an expected 60,300 incident cases, cancer accounted
for 4% of all male diagnoses and 3% of all female diagnoses. Leukemia accounts for 29% of all
childhood malignancies. The projected 24,370 leukemia deaths accounted for 4% of all cancer
fatalities in both men and women. Genetics have little effect on the development of leukemia in
the vast majority of cases. However, if a close relative has chronic lymphocytic leukemia, your
chances of developing the disease rise. Prior cancer treatment, genetic abnormalities, exposure
to certain chemicals, smoking, and a family history of the illness are all linked to specific types
of leukemia (Kamath et al., 2019).

Literature Research

The National Cancer Institute's (NCI) SPORE program for Leukemia encourages multidisciplinary
teams to explore the ailment. The SPORE prizes promote collaboration between basic and
clinical/applied scientists. They encourage study into the biological basis of findings made in
cancer patients or at-risk groups, as well as the successful translation of basic scientific
discoveries into therapeutic practice. The Pediatric Immunotherapy Discovery and
Development Network (PI-DDN) is tasked with discovering and characterizing novel
immunotherapy targets, generating experimental models to evaluate the efficacy of
immunotherapies in children with cancer, and producing new immunotherapy drugs. The PI-
DDN was created as part of the Cancer Moonshot. The Fusion Oncoproteins in Childhood
Cancers (FusOnC2) Consortium is also part of the Cancer Moonshot. The collaborating research
teams will increase our understanding of the function of five main fusion oncoproteins that
cause childhood malignancies such as leukemia (Angione et al., 2021).
Summary Table

Authors Title Year Journal Study design and Sample Main findings
setting size
1 Silver et al. Sustained durability of 2009 Haematologica Patients were 229 Significant improvements
responses and enrolled in STI571 in survival for patients
improved progression- 0102 trial and with advanced CML
free and overall received either 400 receiving imatinib therapy
survival with imatinib mg or 600 mg of
treatment for imatinib daily.
accelerated phase and
blast crisis chronic
myeloid leukemia:
long-term follow-up of
the STI571 0102 and
0109 trials.
2 Palandri et Chronic myeloid 2008 Haematologica A phase II trial with 92 Although imatinib
al. leukemia in blast crisis 600 mg of imatinib improved short-term
treated with imatinib per day results for CML patients
600 mg: outcome of in blast crisis, it had no
the patients alive after significant influence on
a 6-year follow-up CML patients' long-term
 survival rates.
3 Cortes et al. A Phase 2 Trial of 2013 New England Ponatinib was given 449 Ponatinib's potent
Ponatinib in Journal of at a starting dosage antileukemic effects were
Philadelphia Medicine of 45 mg per day. seen in all disease stages
Chromosome–Positive The average and mutation statuses.
Leukemias. duration of follow-
up was 15 months
4 Giles et al. Nilotinib is effective in 2012 Leukemia Nilotinib was given 136 Despite the fact that
imatinib-resistant or - to individuals with nilotinib is very effective
intolerant patients myeloid leukaemia for patients with BP CML,
with chronic myeloid in this research (400 innovative medications
leukemia in blastic mg, twice day). are still required owing to
phase this patient population's
poor long-term prognosis.
5 Gökbuget et Blinatumomab for 2018 Blood For up to four 110 The findings suggest that
al. minimal residual cycles, 15 g/m2 of early targeted MRD
disease in adults with blinatumomab was treatment is an effective
B-cell precursor acute administered therapeutic strategy for
lymphoblastic intravenously (IV). patients with B-cell
leukemia precursor ALL, and that
this strategy should be
 tested in other
hematologic cancers as
well.
6 Foà et al. Dasatinib– 2020 England Journal Study performed a 63 The study was successful
Blinatumomab for Ph- of Medicine phase 2 single-group in initiating and
Positive Acute research. Dasatinib consolidating a molecular
Lymphoblastic and glucocorticoids response and prolonging
Leukemia in Adults were given first, life in patients with Ph-
then two cycles of positive ALL, with
blinatumomab. minimum grade 3 or
higher side effects.
7 Niyongere et Frontline 2020 Pharmaceuticals This study looked at 5 In the frontline setting,
al. Blinatumomab in Older the efficacy of blinatumomab appears to
Adults with blinatumomab be well tolerated, safe,
Philadelphia monotherapy in and effective in older
Chromosome-Negative newly diagnosed patients with B-lineage
B-Cell Acute patients with Ph- ALL. Combination
Lymphoblastic negative B-cell ALL therapies have the
Leukemia potential to improve
outcome consistency.
8 Lau et al. Characterization of 2021 Journal of Blinatumomab was 20 Nevertheless, despite the
 relapse patterns in Oncology given to patients fact that blinatumomab is
patients with acute Pharmacy with relapsed, an effective treatment for
lymphoblastic Practice refractory, or B-ALL, extramedullary
leukemia treated with minimum residual recurrence is quite
blinatumomab disease-positive B- common.
ALL from January 1,
2014 to December
31, 2018.
9 Ribera et al. Feasibility and results 2016 Leukemia ALLOLD07 for 56, 53, Subtype-specific
of subtype-oriented Research Philadelphia (Ph)- 21 treatment improved older
protocols in older negative ALL, ALL patients' prognoses.
adults and fit elderly ALLOPH07 for Ph- Ph-negative non-mature
patients with acute positive ALL, and B-cell Acute
lymphoblastic BURKIMAB08 for Lymphoblastic Leukemia
leukemia: Results of mature B-ALL were has the poorest prognosis
three prospective phase II studies for and urgently needs
parallel trials from the 55-year-olds. ED, CR, improved therapy.
PETHEMA group DFS, OS, and toxicity
were assessed.

10 Kantarjian et Blinatumomab versus 2017 New England Individuals with 405 When compared to
al. Chemotherapy for Journal of extensively chemotherapy,
Advanced Acute Medicine pretreated B-cell linatumomab significantly
Lymphoblastic precursor ALL were improved overall survival
Leukemia randomly assigned in adult patients with
to either relapsed or refractory B-
blinatumomab or cell precursor ALL.
standard-of-care
chemotherapy in
this phase 3 multi-
institutional study.
The primary success
metric was total
survival.
Evidence/ Research Gap

There are research gaps in briefing focuses on how Leukemia affects the old, the young, and
persons of diverse races and ethnicities disproportionately; nonetheless, these populations are
generally disregarded in research reports. Long-standing inequities demand immediate fresh
study into their sources and solutions. To enhance care for older patients with acute myeloid
Leukemia (AML), who have a poor prognosis and limited therapeutic choices, two knowledge
gaps may be overcome. Because the first gap suggests communication challenges between
physicians, patients, and their families about end-of-life choices, it is critical for patients to
engage in dialogues about their care preferences early in the course of treatment. The second
void shows how a new medication combination targeting a particular mutation in the IDH-1
gene may enhance AML treatment results while decreasing immune suppression-related side
effects. This might improve patient quality of life while also increasing therapy response
(Khaldoyanidi et al., 2020).
References:

Angione, S. D., Akalu, A. Y., Gartrell, J., Fletcher, E. P., Burckart, G. J., Reaman, G. H., ... &
Stewart, C. F. (2021). Fusion Oncoproteins in Childhood Cancers: Potential Role in
Targeted Therapy. The Journal of Pediatric Pharmacology and Therapeutics, 26(6), 541-
555.

Bernard, S. C., Abdelsamad, E. H., Johnson, P. A., Chapman, D. L., & Parvathaneni, M. (2017).
Pediatric leukemia: Diagnosis to treatment–A review. Journal of Cancer Clinical trials,
2(2), 1.

Cortes, J. E., Kim, D. W., Pinilla-Ibarz, J. L., Le Coutre, P., Paquette, R., Chuah, C., ... & Kantarjian,
H. (2013). A phase 2 trial of ponatinib in Philadelphia chromosome–positive leukemias.
New England Journal of Medicine, 369(19), 1783-1796.

Foà, R., Bassan, R., Vitale, A., Elia, L., Piciocchi, A., Puzzolo, M. C., ... & Chiaretti, S. (2020).
Dasatinib–blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. New
England Journal of Medicine, 383(17), 1613-1623.

Giles, F. J., Kantarjian, H. M., Le Coutre, P. D., Baccarani, M., Mahon, F. X., Blakesley, R. E., ... &
Ottmann, O. G. (2012). Nilotinib is effective in imatinib-resistant or-intolerant patients
with chronic myeloid leukemia in blastic phase. Leukemia, 26(5), 959-962.

Gökbuget, N., Dombret, H., Bonifacio, M., Reichle, A., Graux, C., Faul, C., ... & Bargou, R. C.
(2018). Blinatumomab for minimal residual disease in adults with B-cell precursor acute
lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology,
131(14), 1522-1531.

Kamath, G. R., Tremblay, D., Coltoff, A., Caro, J., Lancman, G., Bhalla, S., ... & Taioli, E. (2019).
Comparing the epidemiology, clinical characteristics and prognostic factors of acute
myeloid leukemia with and without acute promyelocytic leukemia. Carcinogenesis,
40(5), 651-660.
Kantarjian, H., Stein, A., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J. M., ... & Topp, M. S.
(2017). Blinatumomab versus chemotherapy for advanced acute lymphoblastic
leukemia. New England Journal of Medicine, 376(9), 836-847.

Khaldoyanidi, S. K., Hindoyan, A., Stein, A., & Subklewe, M. (2022). Leukemic Stem Cells as a
Target for Eliminating Acute Myeloid Leukemia: Gaps in Translational Research. Critical
Reviews in Oncology/Hematology, 103710.

Lau, K. M., Saunders, I. M., & Goodman, A. M. (2021). Characterization of relapse patterns in
patients with acute lymphoblastic leukemia treated with blinatumomab. Journal of
Oncology Pharmacy Practice, 27(4), 821-826.

Niyongere, S., Sanchez-Petitto, G., Masur, J., Baer, M. R., Duong, V. H., & Emadi, A. (2020).
Frontline blinatumomab in older adults with Philadelphia chromosome-negative B-cell
acute lymphoblastic leukemia. Pharmaceuticals, 13(6), 124.

Ribera, J. M., García, O., Oriol, A., Gil, C., Montesinos, P., Bernal, T., ... & PETHEMA Group.
(2016). Feasibility and results of subtype-oriented protocols in older adults and fit
elderly patients with acute lymphoblastic leukemia: results of three prospective parallel
trials from the PETHEMA group. Leukemia research, 41, 12-20.

Silver, R. T., Cortes, J., Waltzman, R., Mone, M., & Kantarjian, H. (2009). Sustained durability of
responses and improved progression-free and overall survival with imatinib treatment
for accelerated phase and blast crisis chronic myeloid leukemia: long-term follow-up of
the STI571 0102 and 0109 trials. Haematologica, 94(5), 743.