Prognostic features in acute lymphoblastic leukaemia (ALL)

The good prognostic features in childhood ALL are:
▪ age between one and 10
▪ female gender
▪ low white cell count (below 50 x 109/l)
▪ no evidence of central nervous system disease or particular chromosomal abnormalities
▪ complete response to early chemotherapy.
Haemoglobin and platelet counts have not been shown to significantly influence prognosis.

Human T-lymphotropic virus 1

HTLV-1 is endemic to parts of Japan and the Caribbean. The most serious complications are those of T-cell leukaemia and tropical spastic paraparesis but it is also associated with an inflammatory arthritis and polymyositis. Infected women are advised not to breast feed as transmission via breast milk has been described.

Prognosis of acute myeloid leukaemia (AML)

The Cancer and Leukaemia Group B (CALGB) have determined that for patients aged below 60, high dose cytarabine given after induction can double the likelihood of disease-free survival compared to standard intensification. Immunotherapy has no established role in AML, nor dose maintenance therapy.
Certain karyotypes have more favourable prognoses, with improved long-term disease-free survival. These include genetic alterations such as translocations t(8;21) and t(15;17) and an abnormal 16q22. In contrast, all other karyotype abnormalities confer an adverse prognosis. For those patients with AML who appear to have a normal diploid karyotype, the prognosis is somewhere in between. Although, there is some correlation of karyotype with morphology, the association is weak. Karyotype outweighs age in defining prognosis. Bone marrow transplantation is not significantly superior in first remission and the results are significantly influenced by karyotype.

Red cell morphology

Spherocytosis would be associated with auto immune haemolytic anaemia. Schistocytes or red cell fragments would be more in keeping with mechanical red cell destrcution (e.g. thrombotic thrombocytopenia purpura), bite cells occur with oxidative haemolysis (e.g. G6PD deficiency), Burr cells are seen in renal failure and Pappenheimer bodies are seen in thalassasemia.

Chronic Myeloid Leukaemia

It is not unusual nowadays with the advent of routine automated blood counts to pick up a patient with chronic myeloid leukaemia and none of the classical signs of large hepatosplenomegaly. The picture shows an elevated white count with no increase in blast cells and there are myelocytes and metamyelocytes suggestive of chronic phase disease. A bone marrow or peripheral blood cytogenetics should be carried out looking for the Philadelphia chromosome.

Factor V Leiden Gene Mutation

In the absence of a personal thromboembolic history, Warfarin is not indicated - she may develop bleeding on it. However, given the strong family history, one should be concerned that additional thrombophilic problems are present and a full thrombophilia screen should be performed. If the rest of the screen is negative, one should still be cautious because of the family history - there may be thrombophilic tendencies we are yet to discover.

Pregnancy does not need heparin cover in this woman. The presence of Factor V Leiden itself does not prevent the use of the oral contraceptive or HRT, but given the strong family history, the woman should be counselled about the increased risk of thromboembolism versus the potential benefits and her decision documented for future reference.

Idiopathic Thrombocytopenia Purpura (ITP)

Fig 1: Idiopathic Thrombocytopenic Purpura (ITP)

Fig 2: Bruises in ITP.

Platelet transfusions are generally not indicated in patients with ITP because the transfused platelets are destroyed by the patient's antibodies. However, they are indicated when there is significant acute bleeding.

Fig 3: Platelet pool

Other treatments will take longer to work, but may be administered simultaneously.

Castleman’s Disease

Castleman’s disease is a rare lymphoproliferative disorder characterised by angiofollicular lymphoid hyperplasia. Two histological variants are recognised; a hyaline vascular variant and a less common plasma cell variant. Castleman’s disease has germinal centre hyalinisation or atrophy surrounded by concentric layers of lymphocytes with prominent vascular hyperplasia, hyalinisation of small vessels and interfollicular sheets of plasma cells and immunoblasts.

Multicentric Castleman’s disease (MCD) presents with constitutional symptoms including fever, weight loss and night sweats and clinical findings include lymphadenopathy, hepatosplenomegaly and rashes. Investigations frequently reveal microcytic anaemia, hypoalbuminaemia and polyclonal hypergammaglobulinaemia.

Many of the paraneoplastic manifestations of Castleman’s disease are believed to be due to excess interleukin-6 (IL-6) production by the tumour, possibly from the viral IL-6 homologue gene of HHV8.

The best treatment for MCD is not known.

Acute Blood Loss

Acute loss of blood does not lead to any immediate change in the full blood count: haemodilution takes some time to occur, hence the full blood count can never be used to decide whether or not someone has suffered a significant acute haemorrhage. Physical examination will tell you this, the two most reliable signs of intravascular volume depletion being postural hypotension (lying and sitting) and a reduced jugular venous pressure.

Fig 1: Postural Hypotension

Fig 2: Jugular venous pressure (JVP)

Source: Fig 1, Fig 2,