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When it comes to blood cancer patients, general practitioners (GPs) play a major role in all aspects of care – from preventative measures to early detection, shared care during treatment and health screening post-survivorship. Through an in-depth patient case study, find out how GPs can best support this group through the patient journey.
Blood cancers are the malignant proliferation of blood cells, which encompass conditions such as leukaemia, lymphoma and myeloma.
According to the Singapore Cancer Registry, between 2017 to 2021, blood cancers were among the 10 most common cancers in Singapore, with incidences of 5.2% to 7.3% per annum for lymphoid neoplasms and 3.5% per annum for myeloid neoplasms.1
Blood cancers can occur at any age group, although there are some types that occur more commonly in the paediatric population, such as acute lymphoblastic leukaemia (ALL), and some that occur more commonly in the elderly, such as acute myeloid leukaemia (AML).
Primary care support is essential in all aspects of care: from the prevention of cancer, to detection, symptom management, shared care during chemotherapy and survivorship.
The World Health Organization declares that between 30% to 50% of cancers could be preventable, and advocates increasing awareness through screening, reducing exposure to risk factors and lifestyle changes.2
Screening, symptom recognition and prompt referral
The implementation of screening the full blood count and early referrals for unexplained cytopenias or cytosis has at times picked up the early stages of blood cancers.
Additionally, recognising the presentation of constitutional symptoms of fever, night sweats, loss of appetite or loss of weight with a prompt investigation including a full blood count, liver panel or kidney panel has also picked up blood cancers.
Referrals to hospital upon recognition of these symptoms has allowed for timely targeted investigations.
Encouraging the reduction of exposure to tobacco and alcohol, and advocating a balanced diet and physical activity during routine consultation are general measures to reduce cancer risk factors.
Below are some of the symptoms of blood cancer that patients may experience due to the disease, and their causes.
Prolonged or abnormal bleeding
Coagulopathy related to acute promyelocytic leukaemia (APL)
Numbness or weakness
Central nervous system bleed or thrombosis in disseminated intravascular coagulopathy from APL
Thrombocytopenia from bone marrow infiltration
Anaemia from bone marrow infiltration
Weight loss /loss of appetite
Hypermetabolic symptoms of malignancy
Increased risk of infection or from malignancy
Pathological fractures from myelomas or lymphomas
Or organomegaly from lymphoma involvement
Renal failure or hypercalcaemia from myeloma
Mr M, a 57-year-old man, was seen at the polyclinic for symptoms of persistent fever. He had previously gone on holiday and had intermittent fevers during the vacation. When he returned, he was seen at the polyclinic and examined.
There were no overt signs of infection and general examination was normal. He was given paracetamol and asked to rest at home.
Reassessment and investigations
A few days later, he went back to the polyclinic with persistent fever which abated with paracetamol, but returned after four to six hours. This was associated with unintentional weight loss and loss of appetite.
Blood tests were performed which showed the presence of pancytopenia. His haemoglobin level was 8.6x10-9, total white was 1.35x10-9 and platelets were 3.4x10-9.
The patient was referred to the emergency department for further work-up of pancytopenia with constitutional symptoms.
Usually, patients with pancytopenia and unexplained constitutional symptoms will first undergo biochemical and radiological investigations to rule out infection.
If these are all negative, they would be advised to undergo bone marrow studies, in which we send the blood in the bone marrow for examination under a microscope to look for abnormal or malignant cells.
We would also send this blood sample for flow cytometry, molecular testing, next-generation sequencing and genetic testing, and the bone fragment would be sent for pathological examination.
All these tests are done to confirm the diagnosis of haematological malignancies and determine the prognosis.
Diagnosis through investigations
During his inpatient stay, Mr M continued to have unrelenting fevers at a maximum of 40 degrees Celsius. His initial blood works confirmed pancytopenia. He was initiated on antibiotic treatment to treat neutropenic sepsis.
For his persistent pancytopenia, Mr M underwent a bone marrow investigation. This showed the presence of lymphoblasts. Further molecular testing confirmed that he had ALL.
Treatment of blood cancers is based on combination chemotherapy. These regimes incorporate a variety of agents that target different aspects of the malignant blood cell.
The type of treatment can include cytotoxic agents, biologic agents, small molecule inhibitors or immunotherapy.
Aggressive blood cancers
With aggressive cancers like acute leukaemia or certain types of lymphoma, the regime is administered during inpatient stay as the complications of infection, tumour lysis syndrome or severe cytopenia are expected. Immediate treatment would need to be given at short notice.
Less aggressive blood cancers
However, the less aggressive blood cancers like chronic leukaemia, indolent lymphomas and multiple myeloma all have outpatient treatment.
These patients visit our ambulatory treatment unit at regular intervals for their treatment and blood count monitoring. They may also require adjunctive treatment such as bisphosphonates, red cell boosters, white cell boosters or intravenous immunoglobin as outpatients.
Table 2 shows some of the treatments that the patient may be expected to have in the polyclinic.
ADJUNCTIVE OUTPATIENT TREATMENT PERFORMED AT CLINICS
Red cell booster
To increase red cells during chemotherapy. The frequency changes depending on the haemoglobin level.
Weekly, fortnightly or monthly
Pegylated granulocyte colony-stimulating factor (G-CSF)
White cell booster
To increase white cells. Usually given at least 24 hours after the last dose of chemotherapy per month.
To increase white cells. Dosage per dose is less than pegylated G-CSF, and is used when only a short boost is needed.
Daily for a specified period of time (such as three to five days)
Mr M was counselled on his diagnosis of ALL and seen by a multidisciplinary inpatient team – consisting of the social worker, dietitian, specialist nurse and medical team.
He was offered a course of chemotherapy HCVAD which consists of high-dose cyclophosphamide, vincristine, doxorubicin, dexamethasone and high-dose methotrexate, along with intrathecal chemotherapy.
During chemotherapy, the GP may be asked to help to monitor some of the side effects of chemotherapy. These are listed in Table 3 below.
CONCURRENT CONDITIONS THAT CAN BE CO-MANAGED IN POLYCLINIC
Some patients may develop steroid-induced diabetes as prednisolone plays a large part in the treatment of lymphomas, myelomas and ALL.
Those who already have diabetes may need to have their dosage altered after starting regular steroids.
Steroid-induced or recormon-induced hypertension is frequently reported, and would need to be monitored.
Some patients may have pain from pathological fractures or mucositis due to chemotherapy or radiotherapy.
They would mostly need some opioids such as tramadol in conjunction with paracetamol to provide basal pain relief.
Some chemotherapy agents such as retinoid acid can cause electrolyte abnormalities which lead to cardiac complications.
Patients may be asked to have electrolytes monitored or replaced.
This is a common side effect of chemotherapy and patients should have antiemetics such as ondansetron or granisetron on standby.
Should vomiting still persist, they could be given metoclopramide.
If there are any signs of dehydration, renal failure or electrolyte abnormalities, they should be referred back to the hospital.
The full blood count is monitored regularly by the haematologist in the outpatient setting.
Should they develop symptomatic anaemia or bleeding in between these appointments and go to the polyclinic, they should be referred back to the hospital for transfusions.
All patients on chemotherapy should already be on prophylactic antimicrobials.
Should they develop any infections despite this, they would need hospitalisation for intravenous antimicrobials.
Advising patients with persistent side effects
Patients should be advised that should they continue to have these symptoms after treatment has been given, they should go back to the hospital for further investigation and treatment.
They can see the haematologist either as a walk-in case at the National Cancer Centre Singapore, or an admission through the emergency department.
Patients who previously had chemotherapy or stem cell transplants are known to be at a higher risk of developing early metabolic syndrome, early cardiac disease, secondary malignancies or myelodysplastic syndrome.
As blood cancer patients who have responded well are achieving good remission post-chemotherapy and living longer, there is an ongoing plan to transition their care back to the community.
We are currently devising a protocol to actively screen late effects of chemotherapy after hospital survivorship follow-up. In addition to the Healthier SG initiative, this may also include doing yearly full blood counts, early detection and management of metabolic syndrome and yearly screening of endocrinopathies such as hypothyroidism and osteoporosis.
Five years after chemotherapy, Mr M was still in remission and had done well post-treatment.
Survivorship vaccination and screening programme
He underwent the survivorship vaccination and screening programme at the survivorship clinic for five years.
In these clinic settings, the long-term effects of chemotherapy were monitored. These included assessing for:
Surveillance for secondary malignancies
This programme also screens for psychological sequelae of chemotherapy and hospitalisation, promotes regular dental checks, and advises a healthy lifestyle of maintaining a balanced diet, adequate rest, reducing the stressful environment, maintaining exercise and cutting down alcohol and smoking.
Transition back to primary care
As Mr M remained well at the end of this programme, he was transferred to the polyclinic for continued monitoring.
With ongoing advances in treatment options for blood cancers, the hope to achieve long-lasting remission remains high. Therefore, it becomes increasingly important to garner early support from GPs for these blood cancer patients.
GPs play a major role in all aspects of care, from preventative measures to early detection, shared care during the treatment phase and health screening post-survivorship. In the future, we hope to continue this partnership in our fight against blood cancers.
Singapore Cancer Registry Annual Report 2023. National Registry of Diseases Office. Health Promotion Board.
‘World Health Organisation. Preventing cancer.’ Online [cited 28 September 2023]. Available from: https://www.who.int/activites/preventing-cancer.
Dr Esmeralda Teo Chi Yuan was educated in the United Kingdom and graduated from the Imperial College School of Medicine. She did her foundation training at the North London Deanery and her Internal Medicine training at Singapore General Hospital. She completed her fellowship in haematology with a special interest in acute leukaemia and cancer survivorship.
Dr Teo was awarded the National Medical Research Council Clinician Scientist Award to investigate the interplay of synergistic mechanisms in combination chemotherapy for lymphoma and myeloma at the MD Anderson Cancer Centre in Houston, United States. She has been published in several peer-reviewed journals. During this time, she also completed a chaplaincy course and was awarded the Lay Chaplain of the Year Award.
GPs can call the SingHealth Duke-NUS Blood Cancer Centre for appointments at the following hotlines, or click here to visit the website:
Hospital: 6326 6060
Hospital: 6930 6000
KK Women's and
Children's Hospital: 6692 2984
Centre Singapore: 6436 8288