History

Fact Explanation
Age and sex of the patient Leukemia is a group of malignant disease involving leukocyte forming cells in the bone marrow, characterized by defective proliferation and differentiation of these cell lines. These can be of lymphoid or myeloid origin. In acute leukemia the affected cell lines lack differentiation so that there is increased blast cells. In chronic leukemia cell lines may morphologically differentiate but have defective function. Leukemias are generally named according to the cell line involved and degree of cell differentiation. E.g; Acute lymphocytic leukemia, Chronic myeloid leukemia. The increased proliferation of these cell lines lead to suppression of other cell line production in bone marrow giving rise to the array of clinical features seen in leukemia. Malignancies such as acute lymphocytic leukemia(ALL) is commonly seen in children. Acute myeloid leukemia(AML), chronic lymphocytic leukemia(CLL), chronic myeloid leukemia(CML) etc. are most commonly encountered in adults. ALL has poor prognosis if it is in an adult male. CLL and CML has a male predominance.[1][3][6][9]
Fever Fever is a common symptom of leukemia. Classic pyrexia of unknown origin can be seen these patients. But infections should be excluded first because they can be fatal for these patients.[1][3][6][7]
Malaise Is also a constitutional symptom of cancer.[1][6][7]
Loss of weight This is a constitutional symptom associated with cancer.[1][6][7]
Frequent infections Occur due to neutrophil counts seen in patients with acute leukemia or blast phase of chronic leukemia. These patients are at risk of developing various infections such as pneumonia, otitis media, pharyngitis, infections of skin, perianal region and oral cavity etc. caused by bacteria, virus or fungi.[1][6][7]
Symptoms of anemia such as fatigue, weakness/tiredness shortness of breath, palpitations, dizzy or feeling light headed, chest pain etc. These symptoms may occur in the presence of significant anemia. Anemia occurs due to suppressed red blood cell production in the bone marrow. [6][7][10]
Bleeding manifestations Is a symptom commonly associated with lymphoid tumors and also in other hematological malignancies.[4][6][7]
Night sweats Arise due to thrombocytopenia secondary to marrow failure. Patients may present with easy bruising, bleeding gums, nose, small red spots on skin or heavy menstrual bleeds.[1][6][7]
Anorexia Is also a constitutional symptom associated with leukemia.[1][6][7]
Abdominal discomfort May arise in the presence of splenomegaly and/or hepatomegaly.[1][6][7]
Back pain or Joint pain and swelling This can occur with tumor infiltration of spine and joints.[2][8]
Exposure to radiation Past history of exposure high dose radiation is shown to be associated with development of leukemias.[5]
References
  1. ABRAMSON N, MELTON B. Leukocytosis: Basics of Clinical Assessment. Am Fam Physician.[online] 2000 Nov 1;62(9):2053-2060. [viewed on 13 Sep 2014]Available from; http://www.aafp.org/afp/2000/1101/p2053.html
  2. LAST AR, HULBERT K. Chronic Low Back Pain: Evaluation and Management. Am Fam Physician.[online] 2009 Jun 15;79(12):1067-1074.[viewed on 13 Sep 2014] Available from; http://www.aafp.org/afp/2009/0615/p1067.html
  3. ROTH AR. GINA M. BASELLO GM. Approach to the Adult Patient with Fever of Unknown Origin. Am Fam Physician.[online] 2003 Dec 1;68(11):2223-2229.[viewed on 13 Sep 2014] Available from; http://www.aafp.org/afp/2003/1201/p2223.html
  4. VIERA AJ, BOND MM, YATES SW. Diagnosing Night Sweats. Am Fam Physician.[online] 2003 Mar 1;67(5):1019-1024.[viewed on 13 Sep 2014] Available from; http://www.aafp.org/afp/2003/0301/p1019.html
  5. GUNZ FW, ATKINSON HR. Medical Radiations and Leukaemia: A Retrospective Survey Br Med J [online] 1964 Feb 15, 1(5380):389-393 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1813385
  6. WHITBY L. Leukaemia--I. Clinical Features and Diagnosis Br Med J [online] 1951 Dec 22, 2(4746):1513-1515 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2070835
  7. FRAGKANDREA I, NIXON JA, PANAGOPOULOU P. Signs and symptoms of childhood cancer: a guide for early recognition. Am Fam Physician [online] 2013 Aug 1, 88(3):185-92 [viewed 14 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23939697
  8. BECKERS R, UYTTEBROECK A, DEMAEREL P. Acute lymphoblastic leukaemia presenting with low back pain. Eur J Paediatr Neurol [online] 2002, 6(5):285-7 [viewed 14 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12374580
  9. GHIELMINI M, VITOLO U, KIMBY E, MONTOTO S, WALEWSKI J, PFREUNDSCHUH M, FEDERICO M, HOSKIN P, MCNAMARA C, CALIGARIS-CAPPIO F, STILGENBAUER S, MARCUS R, TRNENY M, DREGER P, MONTSERRAT E, DREYLING M, PANEL MEMBERS OF THE 1ST ESMO CONSENSUS CONFERENCE ON MALIGNANT LYMPHOMA. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol [online] 2013 Mar, 24(3):561-76 [viewed 14 September 2014] Available from: doi:10.1093/annonc/mds517
  10. BRILL JR, BAUMGARDNER DJ. Noamocytic Anemia. Am Fam Physician.[online] 2000 Nov 15;62(10):2255-2263. [viewed on 19 Sep 2014]. Available from; http://www.aafp.org/afp/2000/1115/p2255.html

Examination

Fact Explanation
Pallor This is a sign of anemia.[1][8][10]
Jaundice Seen in patients with autoimmune hemolytic anemia complicating CLL. CLL patients have 5-10% increased risk of developing autoimmune complications and commonest of them is autoimmune hemolysis.[12]
Gum hypertrophy Is seen with acute myeloid leukemia with neoplastic cell infiltration of the gum[7]
Petichiae or purpura or ecchymoses Bleeding manifestations result due to thrombocytopenia associated with leukemia or with the development of disseminated intravascular coagulation.[1][8][10]
Palpable lymph nodes Lymphadenopathy is seen when leukemia cells infiltrate the lymph nodes. These lymph nodes will be enlarged, rubbery,firm and usually involve more than one group of nodes.[5][6]
Skin changes Leukemia cutis is a condition which occurs due to leukemic cell infiltration of the skin. It appears as a rash which may or may not accompany other features of leukemia. Acute febrile neutrophilic dermatosis or Sweet's syndrome is a paraneoplastic syndrome that is associated with malignancy. When it comes to leukemia it is commonly seen with acute myelogenous leukemia. This condition presents with acute onset of fever and raised, erythematous, well-demarcated, painful papules and plaques, which are typically seen on the upper extremities, face and neck. Can be associated with other systemic symptoms.Adult T cell leukemia is a rare malignancy which can also present with cutaneous manifestations. [2][3][4]
Hepatomegaly Occurs with neoplastic cell infiltration of the liver. [1][8]
Splenomegaly Occurs with neoplastic cell infiltration of the spleen.[1][8]
Orchidomegaly Is an uncommon manifestation due to neoplastic cell infiltration of the testes. [1][8]
Cranial nerve palsy or features of meningism These arise when the neoplastic cells infiltrate the central nervous system.[9]
Features of Down's syndrome Children with Down syndrome has 10-20 fold increased for development of ALL and AML.[11]
Other signs of anemia such as presence of rapid thready pulse, cardiac flow murmurs etc. These signs indicate of a hyperdynamic circulation and are found in severe anemia. Patient may also develop cardiomegaly and heart failure later.[1][13][14]
References
  1. FRAGKANDREA I, NIXON JA, PANAGOPOULOU P. Signs and symptoms of childhood cancer: a guide for early recognition. Am Fam Physician [online] 2013 Aug 1, 88(3):185-92 [viewed 14 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23939697
  2. LIMDIWALA PG, PARIKH SJ, SHAH JS. Sweet's syndrome. Indian J Dent Res [online] 2014 May-Jun, 25(3):401-5 [viewed 13 September 2014] Available from: doi:10.4103/0970-9290.138358
  3. GRAHAM RL, BURCH M, KRAUSE JR. Adult T-cell leukemia/lymphoma. Proc (Bayl Univ Med Cent) [online] 2014 Jul, 27(3):235-8 [viewed 15 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24982574
  4. ATAY D, TüRKKAN E, BöLüK K. Aleukemic Leukemia Cutis: An Unusual Rash in a Child Turk J Haematol [online] 2014 Jun, 31(2):213-215 [viewed 15 September 2014] Available from: doi:10.4274/Tjh.2013.0019
  5. DUVALL CP, CARBONE PP, BELL WR, WHANG J, TJIO JH, PERRY S. Chronic myelocytic leukemia with two Philadelphia chromosomes and prominent peripheral lymphadenopathy. Blood [online] 1967 Apr, 29(4):Suppl:652-6 [viewed 15 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/5228553
  6. KARPF M. Lymphadenopathy. In: WALKER HK, HALL WD, HURST JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 149. Available from: http://www.ncbi.nlm.nih.gov/books/NBK256/
  7. TJWA E, MATTIJSSEN V. Gingival Hypertrophy and LeukemiaN Engl J Med 2008; 359:e21.[online]October 16, 2008[viewed on 15 Sep 2014] Available from; http://www.nejm.org/doi/full/10.1056/NEJMicm064633
  8. WHITBY L. Leukaemia--I. Clinical Features and Diagnosis Br Med J [online] 1951 Dec 22, 2(4746):1513-1515 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2070835
  9. LANINGHAM FH, KUN LE, REDDICK WE, OGG RJ, MORRIS EB, PUI CH. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae Neuroradiology [online] 2007 Nov, 49(11):873-888 [viewed 15 September 2014] Available from: doi:10.1007/s00234-007-0300-7
  10. ABRAMSON N, MELTON B. Leukocytosis: Basics of Clinical Assessment. Am Fam Physician.[online] 2000 Nov 1;62(9):2053-2060. [viewed on 13 Sep 2014]Available from; http://www.aafp.org/afp/2000/1101/p2053.html
  11. XAVIER AC, GE Y, TAUB JW. Down Syndrome and Malignancies: A Unique Clinical Relationship: A Paper from the 2008 William Beaumont Hospital Symposium on Molecular Pathology J Mol Diagn [online] 2009 Sep, 11(5):371-380 [viewed 15 September 2014] Available from: doi:10.2353/jmoldx.2009.080132
  12. ZENT CS, KAY NE. Autoimmune Complications in Chronic Lymphocytic Leukemia (CLL) Best Pract Res Clin Haematol [online] 2010 Mar, 23(1):47-59 [viewed 15 September 2014] Available from: doi:10.1016/j.beha.2010.01.004
  13. MELLAND CH. THE DIAGNOSIS AND TREATMENT OF SEVERE ANAEMIA Br Med J [online] 1909 Jun 5, 1(2527):1347-1349 [viewed 20 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2319435
  14. BRILL JR, BAUMGARDNER DJ. Noamocytic Anemia. Am Fam Physician.[online] 2000 Nov 15;62(10):2255-2263. [viewed on 19 Sep 2014]. Available from; http://www.aafp.org/afp/2000/1115/p2255.html

Differential Diagnoses

Fact Explanation
Acute lymphoblastic leukemia(ALL) Is the commonest malignancy seen in children, particularly in the 1-5 age group. It is rare in adults. Can affect either B or T lymphocyte cell lines. It presents with anemia, recurrent infections and bleeding manifestations due to marrow failure. Hepatosplenomegaly, lymphadenopathy and CNS involvement may also be present.[1]
Acute myeloid leukemia(AML) This is the commonest acute leukemia in adults, incidence increase with age. It is a very rapidly progressive malignancy originating from the marrow myeloid cell lines. AML also present with symptoms and signs similar to ALL but CNS involvement is not common. Gum hypertrophy and skin involvement may be present. [2][6]
Chronic myeloid leukemia(CML) This account for about 15% of leukemia and is seen mostly in adults between 40-60 years of age. It is rare in childhood. It is considered a myeloproliferative disorder with uncontrolled clonal proliferation of myeloid cells. Symptoms are chronic and insidious. Patient may present with fever,night sweats, weight loss, bleeding problems, splenomegaly etc. [3]
Chronic lymphocytic leukemia(CLL) Accounts for about 25-30% of leukemias and is seen in the elderly. Median age at presentation is 65-70 years. It is characterized by monoclonal proliferation of immuno-incompetent B lymphocytes.(T cell CLL is rare.) Symptoms are insidious and majority of people are diagnosed incidentally on routine blood count tests. Patient may have increased infections. anemia, night sweats, weight loss, non-tender lymphadenopathy, hepatosplenomegaly etc. Later may develop autoimmune hemolysis. [4]
Hodgkin's Lymphoma Is caused by malignancy in lymphocytes. These malignant cells mainly accumulate in lymph nodes and cause lymphadenopathy but also seen in peripheral blood. [5]
Non-Hodgkin's Lymphoma These lymphomas may manifest as both nodal and/or extranodal disease.[4]
Aplastic Anemia Presents with pancytopenia and symptoms similar to leukemia.[6]
Myelofibrosis Presents with features similar to leukemia. In this condition there is intense marrow fibrosis and myeloid metaplasia leading to hepatosplenomegaly. [7]
Myelodysplastic Syndrome This is characterized by progressive bone marrow failure and ineffective hematopoiesis leading to pancytopenia and clinical features similar to leukemia. Some patients may later undergo transformation to AML.[6]
Multiple myeloma Is caused by malignant clonal proliferation of B lymphocytes. It can present with clinical features similar to leukemia together with osteolytic bone lesions and paraproteinemia.[8]
References
  1. INCIDENCE OF CHILDHOOD LEUKAEMIA. European environment and health information system; WHO.[online] FACT SHEET 4.1;December 2009[viewed on 15 Sep 2014] Available from; http://www.euro.who.int/__data/assets/pdf_file/0005/97016/4.1.-Incidence-of-childhood-leukaemia-EDITED_layouted.pdf
  2. STEVENS RF. Acute myeloid leukaemia. Br Med Bull [online] 1996 Oct, 52(4):764-77 [viewed 15 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9039730
  3. BACCARANI M, PILERI S, STEEGMANN JL, MULLER M, SOVERINI S, DREYLING M, ESMO GUIDELINES WORKING GROUP. Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol [online] 2012 Oct:vii72-7 [viewed 15 September 2014] Available from: doi:10.1093/annonc/mds228
  4. HUH J. Epidemiologic overview of malignant lymphoma. Korean J Hematol [online] 2012 Jun, 47(2):92-104 [viewed 15 September 2014] Available from: doi:10.5045/kjh.2012.47.2.92
  5. MA J, WANG Y, ZHAO H, LIU S, LI Q, LIN L, YUE Y, WANG X, ZHAO Z, YU Y, ZHANG Y. Clinical characteristics of 26 patients with primary extranodal Hodgkin lymphoma. Int J Clin Exp Pathol [online] 2014, 7(8):5045-50 [viewed 15 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25197377
  6. DQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Health Professional Version. [Updated 2014 Aug 15]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK66019/
  7. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Chronic Myeloproliferative Neoplasms Treatment (PDQ®): Patient Version. 2005 Jan 24 [Updated 2014 Sep 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK65999/
  8. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Health Professional Version. [Updated 2014 Jun 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK65924/

Investigations - for Diagnosis

Fact Explanation
Complete blood count with blood picture White cell counts will often be high but can even be normal or low. Red cell count platelet count and hemoglobin level will usually be low. In acute leukemia blast cells will be seen in blood smear. In chronic myeloid leukemia the whole spectrum of myeloid cells (i.e. neutropils, basophils, eosinophils and myelocytes) will be increased in the blood film. Lymphocytes will be increased in chronic lymphocytic leukemia. [1][11][12]
Bone marrow aspiration and biopsy Bone marrow samples are obtained by aspiration and trephine biopsy. These samples can be examined by staining and light microscope or analyzed by cytogenetic or immunohistochemistry studies.[11][12]
Chest X ray Is a basic test done to detect mediastinal lymph node involvement.[11][12]
Ultra sound scan of abdomen Done to assess liver and spleen.[11][12]
Computed tomography of chest and abdomen Done to detect lymph node involvement in chest and abdomen.[11][12]
Cytogenetic analysis Abnormalities that are looked for includes balanced translocations, deletions of chromosomes, abnormalities of chromosome number etc. Testing for bcr-abl translocation helps to distinguish Philadelphia chromosome positive ALL, which has poor prognosis and Philadelphia chromosome positive CML which has a better prognosis. [2][3][4][11][12]
Immunohistochemical studies Can differentiate the cell line origin of leukemia cells. Absence of myeloperoxidase staining and presence of terminal deoxynucleotidyl transferase (TdT) is essential for diagnosis of ALL. Flow cytometry can be used to further detect lymphoid antigens such as CD3 or CD19. CD13, CD33, CD34, CD11c are some myeloid antigens that can be detected.[3][11][12]
Lumbar puncture Done to detect CNS involvement if clinical evidence raise suspicion of CNS infiltration.[10]
Coagulation studies Pctivated partial thromboplastin time (aPTT), Prothrombin time (PT), fibrinogen levels and fibrin degradation products(D-dimer). Done when there are bleeding manifestations or clinically suspected disseminated intravascular coagulation (DIC). In case of DIC, PT and aPTT will be elevated; platelet count and fibrinogen level decreased and D-dimer level increased.[8][9]
Lactic dehydrogenase level (LDH) Is elevated in conditions where there is increased cell lysis, like in cancer.[11]
Serum uric acid level Will be elevated in leukemia and levels will rise further in response to chemotherapy due to increased cell turn over.[7]
Blood/ urine or other appropriate culture Done if there is suspicion of infections. Antibiotic sensitivity should also be performed. Early detection and prompt treatment of infections is very important in these patients to prevent fatal outcomes.[5][6]
References
  1. BAIN BJ. Diagnosis from the blood smear. N Engl J Med [online] 2005 Aug 4, 353(5):498-507 [viewed 13 September 2014] Available from: doi:10.1056/NEJMra043442
  2. ZUCKERMAN T, ROWE JM. Pathogenesis and prognostication in acute lymphoblastic leukemia F1000Prime Rep [online] :59 [viewed 13 September 2014] Available from: doi:10.12703/P6-59
  3. STAUDT LM. Molecular diagnosis of the hematologic cancers. N Engl J Med [online] 2003 May 1, 348(18):1777-85 [viewed 13 September 2014] Available from: doi:10.1056/NEJMra020067
  4. LEE HJ, THOMPSON JE, WANG ES, WETZLER M. Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectives. Cancer [online] 2011 Apr 15, 117(8):1583-94 [viewed 16 September 2014] Available from: doi:10.1002/cncr.25690
  5. FREI E 3RD, LEVIN RH, BODEY GP, MORSE EE, FREIREICH EJ. The nature and control of infections in patients with acute leukemia. Cancer Res [online] 1965 Oct, 25(9):1511-5 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4285787
  6. NOSARI A. Infectious complications in chronic lymphocytic leukemia. Mediterr J Hematol Infect Dis [online] 2012, 4(1):e2012070 [viewed 13 September 2014] Available from: doi:10.4084/MJHID.2012.070
  7. Prevention and management of tumor lysis syndrome in adults with malignancy. J Adv Pract Oncol [online] 2013 Mar, 4(2):101-6 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25031988
  8. SHARMA S,SHARMA P,TYLER LN.Transfusion of Blood and Blood Products: Indications and Complications. Am Fam Physician.[online] 2011 Mar 15;83(6):719-724.[viewed on13 Sep 2014] Available from; http://www.aafp.org/afp/2011/0315/p719.html BALLAS M, KRAUT EH.
  9. Bleeding and Bruising: A Diagnostic Work-up Am Fam Physician.[online] 2008 Apr 15;77(8):1117-1124..[viewed on13 Sep 2014] Available from; http://www.aafp.org/afp/2008/0415/p1117.html
  10. LANINGHAM FH, KUN LE, REDDICK WE, OGG RJ, MORRIS EB, PUI CH. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae Neuroradiology [online] 2007 Nov, 49(11):873-888 [viewed 16 September 2014] Available from: doi:10.1007/s00234-007-0300-7
  11. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Chronic Myelogenous Leukemia Treatment (PDQ®): Health Professional Version. [Updated 2014 May 23]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK65916/
  12. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Chronic Lymphocytic Leukemia Treatment (PDQ®): Health Professional Version. [Updated 2014 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK66035/

Investigations - Fitness for Management

Fact Explanation
Liver enzyme tests Done to assess liver function prior to initiation of chemotherapy and for liver function monitoring during chemotherapy.[1][2]
Serum creatinine Done to assess renal function prior to initiation of treatment.[3]
Serum electrolytes Done to assess renal function.[3]
Fasting blood sugar Done to detect presence of diabetes mellitus if clinically suspected.[4]
Electrocardiogram Done if the patient has features of cardiac disease or a history of ischaemic heart disease. [6]
2D Echocardiogram Done to assess cardiac function and anatomy in patients with features of cardiac disease, such as murmur,cardiomegaly etc.[5]
References
  1. MATHEWS E, LAURIE T, O'RIORDAN K, NABHAN C. Liver involvement with acute myeloid leukemia. Case Rep Gastroenterol [online] 2008 Mar 14, 2(1):121-4 [viewed 16 September 2014] Available from: doi:10.1159/000120756
  2. RIDRUEJO E, CACCHIONE R, VILLAMIL AG, MARCIANO S, GADANO AC, MANDó OG. Imatinib-induced fatal acute liver failure. World J Gastroenterol [online] 2007 Dec 28, 13(48):6608-111 [viewed 16 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18161937
  3. JANUS N, LAUNAY-VACHER V, BYLOOS E, MACHIELS JP, DUCK L, KERGER J, WYNENDAELE W, CANON JL, LYBAERT W, NORTIER J, DERAY G, WILDIERS H. Cancer and renal insufficiency results of the BIRMA study. Br J Cancer [online] 2010 Dec 7, 103(12):1815-21 [viewed 16 September 2014] Available from: doi:10.1038/sj.bjc.6605979
  4. PATEL P, MACEROLLO A.Diabetes Mellitus: Diagnosis and Screening. Am Fam Physician.[online] 2010 Apr 1;81(7):863-870.[viewed on 20 Sep 2014]Available from; http://www.aafp.org/afp/2010/0401/p863.html
  5. ASHLEY EA, NIEBAUER J. Cardiology Explained. London: Remedica; 2004. Chapter 4, Understanding the echocardiogram. [viewed on Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK2215/
  6. ASHLEY EA, NIEBAUER J. Cardiology Explained. London: Remedica; 2004. Chapter 3, Conquering the ECG. [viewed on 20 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK2214/

Management - General Measures

Fact Explanation
Infection control Educate patient regarding risk of infections and importance of avoiding situations that could transmit infections. Employ barrier nursing, proper hand washing. It is important to look for infections, do appropriate investigations and treat any known infection promptly.[3][5]
Managing bleeding problems If the patient has an overt bleeding manifestation or has symptoms and signs of a central nervous system bleed, do clotting screen and CT/MRI of brain if in doubt. Correct the hemostatic defect immediately with platelets, fresh frozen plasma(FFP) etc. If the patient has hyperviscosity syndrome due to very high white cell counts, leukocyte reduction may have to be considered before transfusion. If patient has extensive bleeding in to skin, venepuncture sites etc or develops acute renal failure suspect disseminated intravascular coagulation(DIC). Do a clotting screen, fibrinogen level and D-dimers level. Find and treat the cause of DIC. Replace platelets, fibrinogen(with cryoprecipitate) and coagulation factors(with FFP). Activated protein C has shown to reduce motality in some cases. In acute promyelocytic leukemia which is the commonest leukemia associated with DIC, use of all trans retinoic acid reduce risk of DIC. [1][2][7][8][9]
Managing tumor lysis syndrome This is caused by massive destruction of white cells leading to accumulation of potassium and urate which leads to acute renal failure. Prevention is based on encouraging high fluid intake with allopurinol pre-cytotoxics, and recombinant uricase can be tried.[1][4][7]
Leukapheresis Involves filtration of excess white cells by a special machine and return of the rest of cells and plasma to body. This is used to treat hyperviscosity syndrome which is due to massively increased leukocyte counts leading to thrombi formation in brain, heart, lungs etc by leukostasis. This methos reduces lekocyte counts immediately but the effect lasts only a short time. [6][7]
Education of patient and family Patient and the family should be educated regarding the diagnosis, staging, prognosis, available treatment options for leukemia and their complications etc. These information should help the patient to take informed decisions regarding the treatment for their condition and also improve compliance. They should also be educated regarding potential complications (e.g; risk of infections), how to recognize them and the importance of seeking immediate medical attention. Patient and family should be encouraged to raise their concerns and seek advice. Any doubts present should be clarified. If the patient is a child parents should be made aware of risks of chemotherapy and radiotherapy in the long term, including the risk of secondary cancer. [10][12]
Counselling and support to family and patient Diagnosis of cancer is a very stressful event to both the patient and the family. Referral to psychologist and counseling should be offered to them. Introduction to support groups and other similar individuals will help them to adjust and respond appropriately to the new changes in life. [10][11][12]
References
  1. GONG J, WU B, GUO T, ZHOU S, HE B, PENG X. Hyperleukocytosis: A report of five cases and review of the literature. Oncol Lett [online] 2014 Oct, 8(4):1825-1827 [viewed 13 September 2014] Available from: doi:10.3892/ol.2014.2326
  2. KARIM F, SHAIKH U, ADIL SN, KHURSHID M. Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre. Singapore Med J [online] 2014 Aug, 55(8):443-7 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25189308
  3. NOSARI A. Infectious complications in chronic lymphocytic leukemia. Mediterr J Hematol Infect Dis [online] 2012, 4(1):e2012070 [viewed 13 September 2014] Available from: doi:10.4084/MJHID.2012.070
  4. SARNO J. Prevention and management of tumor lysis syndrome in adults with malignancy. J Adv Pract Oncol [online] 2013 Mar, 4(2):101-6 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25031988
  5. FREI E 3RD, LEVIN RH, BODEY GP, MORSE EE, FREIREICH EJ. The nature and control of infections in patients with acute leukemia. Cancer Res [online] 1965 Oct, 25(9):1511-5 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4285787
  6. PARRA SALINAS IM, GONZáLEZ RODRIGUEZ VP, GARCíA-ERCE JA. Therapeutic leukapheresis: 9-year experience in a University Hospital. Blood Transfus [online] 2014 Jun 5:1-7 [viewed 13 September 2014] Available from: doi:10.2450/2014.0310-13
  7. ZUCKERMAN T, GANZEL C, TALLMAN MS, ROWE JM. How I treat hematologic emergencies in adults with acute leukemia. Blood [online] 2012 Sep 6, 120(10):1993-2002 [viewed 13 September 2014] Available from: doi:10.1182/blood-2012-04-424440
  8. SHARMA S,SHARMA P,TYLER LN.Transfusion of Blood and Blood Products: Indications and Complications. Am Fam Physician.[online] 2011 Mar 15;83(6):719-724.[viewed on13 Sep 2014] Available from; http://www.aafp.org/afp/2011/0315/p719.html
  9. BALLAS M, KRAUT EH. Bleeding and Bruising: A Diagnostic Work-up Am Fam Physician.[online] 2008 Apr 15;77(8):1117-1124..[viewed on13 Sep 2014] Available from; http://www.aafp.org/afp/2008/0415/p1117.html
  10. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Communication in Cancer Care (PDQ®): Health Professional Version. 2008 Nov 24 [Updated 2014 Aug 20]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK65932/
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Management - Specific Treatments

Fact Explanation
Chemotherapy In acute leukemia the treatment is given in phases as for remission induction, consolidation, central nervous system prophylaxis and maintenance. Remission induction aims to clear the circulation of blast cells and reduce number of blasts in the marrow to normal numbers. Drugs are given as combination regimes and includes chemotherapeutic agents such as vincristine, prednisolone, L-asparaginase, daunorubicin etc. Consolidation aims at clearing 'hidden' blast cells for relapse prevention. CNS prophylaxis aims to clear the blast cells 'hidden' in the CNS(given as intrathecal treatment or high dose intravenous treatment). Maintenance therapy is given in the long term as low dose after consolidation is complete. Chronic myeloid leukemia is usually treated with tyrosine kinase inhibitors(TKI) such as imatinib, which is a specific BCR/ABL tyrosine kinase inhibitor. Hydroxycarbamide can be tried in those intolerant or unresponsive to imatinib. Omacetaxine can be given to treat CML that is resistant to TKIs in use due to presence of T315I mutation. Patients in blast crisis are treated as for acute leukemia. Some of them may benefit from imatinib treatment. Alkylating agents such as chlorambucil, cyclophosphamide together with purine analogs such as fludarabine, pentostatin or corticosteroids or monoclonal antibody rituximab are used to treat cronic lymphocytic leukemia(CLL) to reduce lymphocyte counts and improve marrow function.[1][5][10][11]
Radiotherapy CNS irradiation is given in acute leukemia for CNS prophylaxis. Radiation therapy is also used in chronic leukemia for relief from lymhadenopathy or splenomegaly or bone pain. Whole body low dose of radiation is some times given to clear leukemia cells prior to stem cell transplant.[7][8]
Stem cell transplant(SCT) SCT is the only treatment which provides cure for a number of leukemias. Before the transplant procedure, the patient is usually given a high doses of chemotherapy and/or whole body radiation therapy to clear the leukemia cells. Then the patient receives a transplant of stem cells to restore bone marrow cells. These stem cells are obtained either from peripheral blood or the bone marrow. If taken from blood it is called periheral blood stem cell transplant (PBSCT) or if taken from the bone marrow, a bone marrow transplant(BMT). The stem cells can be an allogeneic stem cell transplant (ASCT) or an autologous stem cell transplant. For an allogeneic transplant, the stem cells are obtained from a HLA matched sibling or a HLA matched unrelated donor. Taking umbilical cord stem cells is another option. In an autologous stem cell transplant, the patient's own stem cells are used. These are harvested from the patient's bone marrow or peripheral blood and are stored while the person is treated with high-dose chemotherapy and/or radiation. After that these are transplanted. Non-myeloablative transplant is an option for older patients who cannot tolerate a standard allogeneic transplant that uses high doses of chemotherapy. These patients are given lower doses of chemotherapy and radiation that do not completely destroy the cells in bone marrow. After this the patient receives the allogeneic stem cells that establish a new immune system and destroy the leukemia cells(graft-versus-leukemia effect).[1][2][3][4][6]
Splenectomy Is done for symptomatic relief in patients with massive enlarged spleens, not shrunk by chemotherapy or radiation. It may also improve platelet and red cell counts and lower the need for transfusions. [9][14]
References
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  2. HELBIG G, KRAWCZYK-KULIS M, KOPERA M, JAGODA K, RZEPKA P, MAJEWSKA-TESSAR A, HEJLA M, KYRCZ-KRZEMIEN S. Autologous Hematopoietic Stem Cell Transplantation for High-risk Acute Lymphoblastic Leukemia: non-Randomized Study with a maximum Follow-up of more than 22 Years. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014047 [viewed 13 September 2014] Available from: doi:10.4084/MJHID.2014.047
  3. HEIDEGGER S, VAN DEN BRINK MR, HAAS T, POECK H. The role of pattern-recognition receptors in graft-versus-host disease and graft-versus-leukemia after allogeneic stem cell transplantation. Front Immunol [online] 2014:337 [viewed 13 September 2014] Available from: doi:10.3389/fimmu.2014.00337
  4. OUDIN C, CHEVALLIER P, FURST S, GUILLAUME T, EL CHEIKH J, DELAUNAY J, CASTAGNA L, FAUCHER C, GRANATA A, DEVILLIER R, CHABANNON C, ESTERNI B, VEY N, MOHTY M, BLAISE D. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies. Haematologica [online] 2014 Aug 1 [viewed 13 September 2014] Available from: doi:10.3324/haematol.2014.105981
  5. RIBERA JM, RIBERA J, GENESCà E. Treatment of adolescent and young adults with acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis [online] 2014, 6(1):e2014052 [viewed 13 September 2014] Available from: doi:10.4084/MJHID.2014.052
  6. ALJOHANI NI, THOMPSON K, HASEGAWA W, WHITE D, KEW A, COUBAN S. Non-myeloablative allogeneic hematopoietic transplantation for patients with hematologic malignancies: 9-year single-centre experience. Curr Oncol [online] 2014 Jun, 21(3):e434-40 [viewed 13 September 2014] Available from: doi:10.3747/co.21.1846
  7. KING D. Radiotherapy in the Management of Leukemia Can Med Assoc J [online] 1967 Jun 24, 96(25):1621-1625 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1923077
  8. MOTT MG. Irradiation of C.N.S. in leukemia. Br Med J [online] 1973 Sep 15, 3(5880):590 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4726934
  9. SUBBIAH V, VINY AD, ROSENBLATT S, POHLMAN B, LICHTIN A, MACIEJEWSKI JP. Outcomes of splenectomy in T-cell large granular lymphocyte leukemia with splenomegaly and cytopenia. Exp Hematol [online] 2008 Sep, 36(9):1078-83 [viewed 13 September 2014] Available from: doi:10.1016/j.exphem.2008.04.005
  10. ARELLANO M, PAKKALA S, LANGSTON A, TIGHIOUART M, PAN L, CHEN Z, HEFFNER LT, LONIAL S, WINTON E, KHOURY HJ. Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia. Cancer [online] 2012 Nov 1, 118(21):5278-82 [viewed 13 September 2014] Available from: doi:10.1002/cncr.27494
  11. BAROUCH-BENTOV R, SAUER K. Mechanisms of drug resistance in kinases. Expert Opin Investig Drugs [online] 2011 Feb, 20(2):153-208 [viewed 13 September 2014] Available from: doi:10.1517/13543784.2011.546344
  12. SUTTORP M, MILLOT F. Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program [online] 2010:368-76 [viewed 13 September 2014] Available from: doi:10.1182/asheducation-2010.1.368
  13. FERRAJOLI A. Treatment of younger patients with chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program [online] 2010:82-9 [viewed 13 September 2014] Available from: doi:10.1182/asheducation-2010.1.82
  14. MUSSER G, LAZAR G, HOCKING W, BUSUTTIL RW. Splenectomy for hematologic disease. The UCLA experience with 306 patients. Ann Surg [online] 1984 Jul, 200(1):40-5 [viewed 15 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6732325