Acute lymphoblastic leukemia natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Carlos A Lopez, M.D. [3]

Overview

Prognosis has improved from a 0% to 20-75% survival rate largely due to the continuous development of clinical trials and improvements in bone marrow transplantation (BMT) and stem cell transplantation (SCT) technology. The prognosis for acute lymphoblastic leukemia differs between individuals depending on a wide variety of factors such as gender, ethnicity, age, blood cell count, dissemination and genetic involvement.

Natural History, Complications, and Prognosis

Natural history

If left untreated, of patients with acute lymphoblastic leukemia may progress to develop infection, bleeding, infertility, and metastasis to other organs.[1][2][3][4]

Prognosis

  • The overall cure rate in children is 85%, and about 50% of adults have long-term disease-free survival.[5][6]
  • It is worth noting that medical advances in recent years, both through matching the best treatment to the genetic characteristics of the blast cells and through the availability of new drugs, are not fully reflected in statistics that usually refer to five-year survival rates.
  • The prognosis for acute Lymphoblastic leukemia differs between individuals depending on a wide variety of factors:

Gender

  • Females tend to fare better than males[9]

Ethnicity

  • Caucasians are more likely to develop acute leukemia than African-Americans, Asians and Hispanics and tend to have a better prognosis than non-Caucasians.

Age

  • Age is a significant factor in children with acute lymphoblastic leukemia and may be an important prognostic factor in adult with acute lympoblastic leukemia as well[10]
  • In one study, overall the prognosis was better in patients younger than 25 years; another study found a better prognosis in patients younger than 35 years
  • These findings may in part, be related to the increased incidence of the Ph1 in older acute lymphoblatic leukemia patients a subgroup associated with poor prognosis
  • Children between 1-10 years of age are most likely to be cured.

Blood cell count

  • White blood cell count at diagnosis of less than 50,000/µl.

Dissemination

Genetic involvement

Cytogenetic subtypes with worse prognosis

Central nervous system involvement

  • As in childhood acute lymphoblastic leukemia, adult patients with acute lymphoblastic luekemia are at risk of developing central nervous system involvement during the course of their disease. This is particularly true for patients with L3 (Burkitt) morphology. Both treatment and prognosis are influenced by this complication.

Celular morphology

  • Patients with L3 morphology showed improved outcomes, as evidenced in a completed cancer and Leukemia Group B study, when treated according to specific treatment algorithms. This study found that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like chemotherapy regimens.

5 Year survival

  • Between 2004 and 2010, the 5-year relative survival of patients with acute lymphoblastic leukemias was 70%.[16]
  • When stratified by age, the 5-year relative survival of patients with acute lymphoblastic leukemias was 71.3% and 12.2% for patients <65 and ≥ 65 years of age respectively.[16]

References

  1. Ma X, Urayama K, Chang J, Wiemels JL, Buffler PA (2009). "Infection and pediatric acute lymphoblastic leukemia". Blood Cells Mol. Dis. 42 (2): 117–20. doi:10.1016/j.bcmd.2008.10.006. PMC 2834409. PMID 19064328.
  2. Byrne J, Fears TR, Mills JL, Zeltzer LK, Sklar C, Meadows AT, Reaman GH, Robison LL (April 2004). "Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood". Pediatr Blood Cancer. 42 (4): 364–72. doi:10.1002/pbc.10449. PMID 14966835.
  3. Shigeta H, Tasaki N, Kitazumi S, Kitagawa Y, Kanatsuna T, Kondo M (April 1987). "[A case report of Bartter's syndrome associated with possible pseudohypoparathyroidism type II]". Nippon Naika Gakkai Zasshi (in Japanese). 76 (4): 549–52. PMID 3611913.
  4. Harrison's Principles of Internal Medicine, 16th Edition, Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.
  5. "National Cancer Institute".
  6. Barrett AJ (June 1994). "Bone marrow transplantation for acute lymphoblastic leukaemia". Baillieres Clin. Haematol. 7 (2): 377–401. PMID 7803908.
  7. Bishop MR, Logan BR, Gandham S, Bolwell BJ, Cahn JY, Lazarus HM, Litzow MR, Marks DI, Wiernik PH, McCarthy PL, Russell JA, Miller CB, Sierra J, Milone G, Keating A, Loberiza FR, Giralt S, Horowitz MM, Weisdorf DJ (April 2008). "Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research". Bone Marrow Transplant. 41 (7): 635–42. doi:10.1038/sj.bmt.1705952. PMC 2587442. PMID 18084335.
  8. Pui CH, Boyett JM, Relling MV, Harrison PL, Rivera GK, Behm FG; et al. (1999). "Sex differences in prognosis for children with acute lymphoblastic leukemia". J Clin Oncol. 17 (3): 818–24. doi:10.1200/JCO.1999.17.3.818. PMID 10071272.
  9. Foà R (2011). "Acute lymphoblastic leukemia: age and biology". Pediatr Rep. 3 Suppl 2: e2. doi:10.4081/pr.2011.s2.e2. PMC 3206534. PMID 22053278.
  10. Mowery CT, Reyes JM, Cabal-Hierro L, Higby KJ, Karlin KL, Wang JH; et al. (2018). "Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression". Cell Rep. 25 (7): 1898–1911.e5. doi:10.1016/j.celrep.2018.10.061. PMC 6321629. PMID 30428356.
  11. Koo HH (2011). "Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood". Korean J Pediatr. 54 (3): 106–10. doi:10.3345/kjp.2011.54.3.106. PMC 3120995. PMID 21738539.
  12. Nashed AL, Rao KW, Gulley ML (2003). "Clinical applications of BCR-ABL molecular testing in acute leukemia". J Mol Diagn. 5 (2): 63–72. doi:10.1016/S1525-1578(10)60454-0. PMC 1907317. PMID 12707370.
  13. Fielding AK (January 2010). "Current treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia". Haematologica. 95 (1): 8–12. doi:10.3324/haematol.2009.015974. PMC 2805747. PMID 20065078.
  14. Mullighan CG (2012). "Molecular genetics of B-precursor acute lymphoblastic leukemia". J Clin Invest. 122 (10): 3407–15. doi:10.1172/JCI61203. PMC 3461902. PMID 23023711.
  15. 16.0 16.1 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.

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