Discussion:
XP is a rare autosomal recessive disease with 100% penetrance. Patients
have sensitivity to ultraviolet (UV) radiation, thereby increasing the
risk of cutaneous tumours, such as squamous cell carcinoma (SCC), basal
cell carcinoma (BCC), and cutaneous melanoma (CM).1The most common cause of death in XP patients is skin cancer5
Normal individuals harbouring XPD polymorphisms are at increased risk
for developing acute leukaemia. In a study by ElMahgoub IR et.al, which
evaluated polymorphisms of xeroderma pigmentosum genes (XPC, XPD, and
XPG) and susceptibility to acute leukaemia among a sample of Egyptian
patients, homovariant for XPD had four fold increased risk of developing
AML (OR = 4.4, P = 0.025) either alone or with variant genotypes of XPC
and XPG.6
The published cases of XP with haematological malignancies are
summarised in table 1. Most of the patients were adolescents, with the
youngest being a 7 year old with B-ALL with MDS. Death due to leukaemia
and treatment related toxicity were observed in all patients except for
one.
Treatment of hematologic malignancies in patients with defective DNA
repair pathways requires careful consideration.8Patients with XP generally tolerate diagnostic X-rays and
radiotherapy.9 However, sensitivity to certain
chemotherapies depends on the specific NER deficiency.10
Sumiyoshi et.al11, reported 2 cases of adults with XP,
who were relatives, treated using cisplatin for papillary-predominant
adenocarcinoma and squamous cell carcinoma of oesophagus. Both of them
had enhanced adverse reactions and antitumor activity. The first patient
developed diarrhoea, vomiting, transaminitis, hyperbilirubinemia, acute
kidney injury (AKI) requiring haemodialysis and complete hearing loss.
The second patient developed hearing impairment requiring hearing aid,
AKI and severe myelosuppression, leading to death.
In contrast to these reports, our paediatric patient tolerated induction
ALL chemotherapy relatively well. Even though there was transient
derangement of liver function tests during induction, Pseudomonas sepsis
and oral mucositis during protocol M and hyperbilirubinemia during
maintenance, he remains disease free at 26 months from diagnosis.