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{{Acute lymphoblastic leukemia}}
{{Acute lymphoblastic leukemia}}


{{CMG}} {{AE}} {{RT}}
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==Overview==
==Overview==
[[Prognosis]] has improved from a 0% to 20-75% survival rate largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation ([[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.<ref name="urlInfection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003 | Blood Journal">{{cite web |url=http://www.bloodjournal.org/content/124/7/1056?sso-checked=true |title=Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003 &#124; Blood Journal |format= |work= |accessdate=}}</ref><ref name="pmid19064328">{{cite journal |vauthors=Ma X, Urayama K, Chang J, Wiemels JL, Buffler PA |title=Infection and pediatric acute lymphoblastic leukemia |journal=Blood Cells Mol. Dis. |volume=42 |issue=2 |pages=117–20 |date=2009 |pmid=19064328 |pmc=2834409 |doi=10.1016/j.bcmd.2008.10.006 |url=}}</ref><ref name="pmid14966835">{{cite journal |vauthors=Byrne J, Fears TR, Mills JL, Zeltzer LK, Sklar C, Meadows AT, Reaman GH, Robison LL |title=Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood |journal=Pediatr Blood Cancer |volume=42 |issue=4 |pages=364–72 |date=April 2004 |pmid=14966835 |doi=10.1002/pbc.10449 |url=}}</ref><ref name="pmid3611913">{{cite journal |vauthors=Shigeta H, Tasaki N, Kitazumi S, Kitagawa Y, Kanatsuna T, Kondo M |title=[A case report of Bartter's syndrome associated with possible pseudohypoparathyroidism type II] |language=Japanese |journal=Nippon Naika Gakkai Zasshi |volume=76 |issue=4 |pages=549–52 |date=April 1987 |pmid=3611913 |doi= |url=}}</ref>


== Natural History==
===Prognosis===
*The overall cure rate in children is 85%, and about 50% of adults have long-term disease-free survival.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th Edition,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref><ref name="ALL">{{cite web | title = National Cancer Institute| url =http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq }}</ref>


==Complications==
*Advancements in medical [[Medical technology|technology]] and [[research]] over the past four decades in the treatment of acute lymphocytic leukemia has improved the overall [[prognosis]] significantly from a 0% to 20-75% survival rate
*Largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation (BMT) and [[stem cell transplantation]] (SCT) technology.<ref name="pmid7803908">{{cite journal |vauthors=Barrett AJ |title=Bone marrow transplantation for acute lymphoblastic leukaemia |journal=Baillieres Clin. Haematol. |volume=7 |issue=2 |pages=377–401 |date=June 1994 |pmid=7803908 |doi= |url=}}</ref><ref name="pmid18084335">{{cite journal |vauthors=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 |title=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 |journal=Bone Marrow Transplant. |volume=41 |issue=7 |pages=635–42 |date=April 2008 |pmid=18084335 |pmc=2587442 |doi=10.1038/sj.bmt.1705952 |url=}}</ref>


==Prognosis ==
*It is worth noting that medical advances in recent years, both through matching the best treatment to the [[Genetics|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 overall cure rate in children is 85%, and about 50% of adults have long-term disease-free survival.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th Edition,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref>
*The [[prognosis]] for acute Lymphoblastic leukemia differs between individuals depending on a wide variety of factors:


Advancements in medical [[Medical technology|technology]] and [[research]] over the past four decades in the treatment of ALL has improved the overall prognosis significantly from a zero to 20-75 percent survival rate, largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation (BMT) and [[stem cell transplantation]] (SCT) technology.
===Gender===
* Females tend to fare better than males<ref name="pmid10071272">{{cite journal| author=Pui CH, Boyett JM, Relling MV, Harrison PL, Rivera GK, Behm FG et al.| title=Sex differences in prognosis for children with acute lymphoblastic leukemia. | journal=J Clin Oncol | year= 1999 | volume= 17 | issue= 3 | pages= 818-24 | pmid=10071272 | doi=10.1200/JCO.1999.17.3.818 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10071272  }} </ref>


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 ALL differs between individuals depending on a wide variety of factors:
===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<ref name="pmid22053278">{{cite journal| author=Foà R| title=Acute lymphoblastic leukemia: age and biology. | journal=Pediatr Rep | year= 2011 | volume= 3 Suppl 2 | issue=  | pages= e2 | pmid=22053278 | doi=10.4081/pr.2011.s2.e2 | pmc=3206534 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22053278  }} </ref>
*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.


* Gender: Females tend to fare better than males.
===Blood cell count===
* 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.
* White blood cell count at diagnosis of less than 50,000/µl.
* Age at diagnosis: children between 1-10 years of age are most likely to be cured.
===Dissemination===
* White blood cell count at diagnosis of less than 50,000/µl
* Whether the [[cancer]] has spread to the [[brain]] or [[spinal cord]]
* Whether the [[cancer]] has spread to the [[brain]] or [[spinal cord]]
* Morphological, immunological, and genetic subtypes
===Genetic involvement===
* Response of patient to initial treatment
* [[Down syndrome|Down's Syndrome]] tend to have a [[genetic]] involvement <ref name="pmid30428356">{{cite journal| author=Mowery CT, Reyes JM, Cabal-Hierro L, Higby KJ, Karlin KL, Wang JH et al.| title=Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression. | journal=Cell Rep | year= 2018 | volume= 25 | issue= 7 | pages= 1898-1911.e5 | pmid=30428356 | doi=10.1016/j.celrep.2018.10.061 | pmc=6321629 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30428356  }} </ref>
* [[Genetic disorder]]s such as [[Down syndrome|Down's Syndrome]]
* [[Chromosomal]] abnormalities: [[Chromosomal]] abnormalities including [[aneuploidy]] and translocations, have been described and may correlate with [[prognosis]]
*In particular, patients with Ph1-positive t(9;22) acute lymphoblastic leukemia have a poor [[prognosis]] and represent more than 30% of adult cases<ref name="pmid21738539">{{cite journal| author=Koo HH| title=Philadelphia chromosome-positive acute lymphoblastic leukemia in childhood. | journal=Korean J Pediatr | year= 2011 | volume= 54 | issue= 3 | pages= 106-10 | pmid=21738539 | doi=10.3345/kjp.2011.54.3.106 | pmc=3120995 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21738539  }} </ref>
*[[Bcr-abl]]-rearranged leukemias that do not demonstrate the classical Ph1 carry a poor [[prognosis]] that is similar to those that are [[Philadelphia chromosome|Ph1-positive]]<ref name="pmid12707370">{{cite journal| author=Nashed AL, Rao KW, Gulley ML| title=Clinical applications of BCR-ABL molecular testing in acute leukemia. | journal=J Mol Diagn | year= 2003 | volume= 5 | issue= 2 | pages= 63-72 | pmid=12707370 | doi=10.1016/S1525-1578(10)60454-0 | pmc=1907317 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12707370  }} </ref>
*Patients with Ph1-positive acute lymphoblastic leukemias are rarely cured with [[chemotherapy]], although long-term survival is now being routinely reported when such patients are treated with combinations of [[chemotherapy]] and [[Bcr-abl]] [[tyrosine kinase inhibitors]]<ref name="pmid20065078">{{cite journal |vauthors=Fielding AK |title=Current treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia |journal=Haematologica |volume=95 |issue=1 |pages=8–12 |date=January 2010 |pmid=20065078 |pmc=2805747 |doi=10.3324/haematol.2009.015974 |url=}}</ref>
*Two other [[chromosomal]] abnormalities with poor [[prognosis]] are t(4;11), which is characterized by rearrangements of the [[myeloid]] [[lymphoid]] [[leukemia]] [[gene]] and may be rearranged despite normal [[cytogenetics]], and t(9;22)<ref name="pmid23023711">{{cite journal| author=Mullighan CG| title=Molecular genetics of B-precursor acute lymphoblastic leukemia. | journal=J Clin Invest | year= 2012 | volume= 122 | issue= 10 | pages= 3407-15 | pmid=23023711 | doi=10.1172/JCI61203 | pmc=3461902 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23023711  }} </ref>
*In addition to t(4;11) and [[Philadelphia chromosome|t(9;22)]], compared with patients with a normal [[karyotype]], patients with deletion of [[chromosome 7]] or [[trisomy 8]] have been reported to have a lower probability of survival at 5 years
*In a multivariate analysis, [[karyotype]] was the most important predictor of disease-free survival.


Some cytogenetic subtypes have a worse prognosis than others. These include:
===Cytogenetic subtypes with worse prognosis===
* A translocation between [[chromosome]]s 9 and [[Chromosome 22|22]], known as the [[Philadelphia chromosome]], occurs in about 20% of adult and 5% in pediatric cases of acute lymphoblastic luekemia.
* A translocation between [[Chromosome 4|chromosomes 4]] and [[Chromosome|11]] occurs in about 4% of cases and is most common in [[infants]] under 12 months.
* Not all [[translocations]] of [[chromosomes]] carry a poorer [[prognosis]]. Some [[translocations]] are relatively favorable. For example, hyperdiploidy (>50 [[chromosomes]]) is a good [[prognostic]] factor.


* A translocation between [[chromosome]]s 9 and 22, known as the [[Philadelphia chromosome]], occurs in about 20% of adult and 5% in pediatric cases of ALL.
===Central nervous system involvement===
* A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.
* 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's lymphoma|Burkitt]]) morphology. Both treatment and [[prognosis]] are influenced by this complication.
* Not all translocations of chromosomes carry a poorer prognosis. Some translocations are relatively favorable. For example, Hyperdiploidy (>50 chromosomes) is a good prognostic factor.
 
===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%.<ref name="SEER">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.</ref>
 
* 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.<ref name="SEER">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.</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Lymphocytic leukemia]]
[[Category:Leukemia]]


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Latest revision as of 15:44, 29 October 2019

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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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