Acute Leukaemia |blood cancer

 Introduction and Epidemiology

Leukaemias are a heterogenous group of cancers arising from blood cells that involve  the bone marrow and peripheral blood, and may be lymphoid or myeloid.

It is broadly  categorized into acute leukaemia and chronic leukaemia.

Acute leukaemia is characterized by the presence in the bone marrow and/or peripheral  blood circulation of immature cells (blast or promyelocytes).

Lymphoblasts are found  in acute lymphoblastic leukaemia (ALL) while myeloblasts are found in acute myeloid  leukaemia (AML).

Both myeloblasts and promyelocytes are found in a subset of AML  knowns as acute promyelocetic leukaemia (APML).

All have aggressive biological behavior  with rapid progression to fatality if not properly treated.

Epidemiology.

Even though acute myeloid leukemias (AMLs) are infrequent they are highly malignant yet curable in a sizeable proportion of cases it treated appropriately making them  significant in clinical practice. 

AML shows 2 peaks in occurrence, one in early childhood with the majority occurring later  in adulthood. 

ALL is on the other hand most common in childhood with a peak incidence at 2–5 years  of age, with a smaller peak in old age.
There is a slight male preponderance in both AML and ALL.

 Diagnosis

Patients with the following symptoms (history) should be further evaluated

  •  Recurrent infections.
  •  Bleeding or easy bruisability.
  •  Unexplained Weight loss.
  •  Drenching night sweats.
  •  Persistent fever.
  • Bone pains.

The following clinical signs should be looked for in a full physical examination:

  •  Pallor (anaemia).
  •  Splenomegaly.
  •  Hepatomegally.
  •  Bruising (purpura).
  • Gum hypertrophy.
  • Lymphadenopathy (All groups of lymph nodes.

Laboratory Evaluation.

• Bone Marrow Aspirate (mandatory) and trephine (recommended) for diagnosis, with relevant cytochemistry and immunophenotyping as applicable.

• FBC, with differential count and peripheral blood film examination

~ Where the blood count is abnormal, or there are abnormal cells are  seen on peripheral film, the slides must be reviewed by a specialist pathologist 
(haematopathologist or clinical pathologist with haematology experience)

Stained slides and unstained slides should be prepared at site and sent with  the whole blood to the pathology laboratory for review, if initially reported by a technologist only

.• Biochemistry including liver and renal function tests, alkaline phosphatase (ALP),  lactate dehydrogenase (LDH), urate, and liver enzymes.

• Viral serology for HIV (mandatory), Hepatitis B and Hepatitis C (strongly recommended).

• Diagnostic tap (Lumbar puncture) is mandatory for all patients with ALL, and   is recommended for other acute leukaemias with clinical suspicion of CNS 
 involvement.

 Radiology & Imaging

Generally not required, but may be guided by the clinical presentation.

• The following ancillary tests are recommended where possible: flow cytometry/ immunophenotyping and cytogenetics/molecular studies are recommended 
 for establishing sub-type of acute leukaemia for purposes of risk stratification and  prognostication.

Staging and risk assessment

• Biochemistry including liver and renal function tests, alkaline phosphatase (ALP),  lactate dehydrogenase (LDH), urate, and liver enzymes.

• Viral serology for HIV (mandatory), Hepatitis B and Hepatitis C (strongly recommended).

• Diagnostic tap (Lumbar puncture) is mandatory for all patients with ALL, and   is recommended for other acute leukaemias with clinical suspicion of CNS 
 involvement.

 

 Radiology & Imaging.

Generally not required, but may be guided by the clinical presentation.

Management

Treatment is divided into supportive and definitive treatment

Supportive Treatment.

• Treatment of infections with relevant antimicrobial agents.

• Provision of prophylactic antimicrobials at a specialized centre.

• Transfusion of blood components (packed cells and platelet concentrates) as needed.

• Hydration.

Correction of abnormal blood chemistries such as hyperuricaemia, lactic acidosis and renal failure.

• Prevention and management of tumour lysis syndrome.

Specific Treatment.

The treatment is stratified according to the specific type of acute leukaemia, and it is recommended that such treatment should only be initiated by an oncology specialist at a specialized treatment center.

AML other than APML.

Treatment options include induction and consolidation chemotherapy with a curative intent.

Patients older than 65 years are more susceptible to treatment complications than young patients because of other co-morbidities such as diabetes mellitus, hypertension and coronary artery disease.

• Induction:
~ Chemotherapy regimen options includes Cytarabine, Anthracyclines (e.g. 
Daunorubicin) in 7+3 regimen as the standard recommended regimen

• Consolidation:
~ Involves use of high-dose cytarabine (HIDAC) which has various  toxicities including non-haematological toxicities such as cerebellar ataxia that 
should prompt immediate discontinuation of the chemotherapy.

Steroidal eye  drops must be instilled from the initiation of therapy.

APML.

APML (AML M3) is treated differently from other AMLs. 

The treatment includes induction with differentiation agents like all trans retinoic acid (atra®) and anthracyclines (such as daunorubicin) which should be given as emergency treatment by a specialist at a specialist treatment centre.

These patients are at high risk for developing life threatening coagulopathies hence the need for prompt consultation 
to a specialist and referral to a specialist centre. 

Maintenance therapy is part of standard of care for APML, and may go up to 24 months, 
given by a specialist.

If promptly diagnosed and therapy initiated early, this is the AML with the best prognosis.

Arsenic trioxide should be considered for relapsed APML.

A.L.L

Treatment of ALL follows the same pattern of induction, consolidation, CNS prophylaxis and maintenance chemotherapy.

There are various and varying protocols for treatment  for ALL available.

Owing to high toxicity of these regimens, supportive therapy is paramount in the  management, hence the need for prompt and continued care at a specialized referral centre during and after treatment.

Radiation therapy for CNS prophylaxis is recommended after consolidation/during maintenance.

Relapsed or Refractory Disease.

Management of relapses depends on the specific sub-type of the acute leukaemia, and  this should be referred to a specialist at a specialized cancer treatment center for salvage  chemotherapy, and consideration for bone marrow stem cell transplant where possible.

 Pharmacological management

Anthracyclines and anthracenediones, cytosine arabinoside, methotrexate, etoposide, 6-thioguaunine, 6-mercaptopurine, cyclophosphamide, vincristine, L-asparaginase,  prednisone/prednisolone, dexamethasone.

In resource limited settings, a combination of doxorubicin or daunorubicin, vincristine,  cytosine arabinoside and prednisone is commonly used.

Where resources are available,  other combinations such as the United Kingdom Acute Leukaemia (UKAL), Linker, Cancer  and Leukaemia Group B (CALGB) and Hyper-fractionated cylophosphomide, vincristine, adriamycin HD dexamethasone (Hyper-CVAD) [+ or – high dose methotrexate and high 
dose cytosine arabinoside] amongst others, are used.

These combinations can only be administered in specialized centers with adequate support facilities.

 Prognosis

Childhood ALL is curable in a majority of cases if treated appropriately wheres adult ALL  carries almost as poor a prognosis as AML. 

References

  1. Othieno Abinya NA. Drug Treatment in Neoplastic Disorders of The Haematopoietic and lymphoreticular System. Jomo Kenyatta Foundation 2006.
  2. .Appelbaum FR, Kopecky KJ, Tallman MS, et al. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br j Haematol 2006;135:165-173
  3. Wiernik PH, Banks PL, Case DC, Jr., et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukaemia. Blood 1992;79:313-319
  4. Cassileth PA, Hines JD, Oken MM, et al. Maintenance chemotherapy  prolongs remission duration in adult acute nonlymphocytic leukaemia. J Clin Oncol 1998;6:583-587
  5. .Tallman MS, Nabhan C, Feusner JH, et al. Acute promyelocytic leukaemia: Evolving therapeutic strategies. Blood 2002;99:759-767
  6. .Pui CH, Relling MV, Downing JR, et al. Acute lymphoblastic leukaemia. N  Engl J Med 2004;350:1535-1548
  7. .Bishop JF, Matthews JP, Young GA, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukaemia. Blood 1996;87(1710-1717.
  8. Othieno-Abinya N.A., Nyabola L.O. The prognosis of adult acute leukaemias at Kenyatta National Hospital in the 1980s. Discovery and Innovation 1991; 3: 95.

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