Miss Nikita Mepani 30th July 1992 - 20th July 2012. Past away before her time.
The Association of Inflammatory Bowel Disease and Leukemia-Coincidence or Not?
Start of illness and medications
Azathioprine may increase your risk of developing certain types of cancer, especially skin cancer and lymphoma (cancer that begins in the cells that fight infection).
Adding infliximab (Remicade) to azathioprine increases the risk of lymphoma dramatically, and because of the risk, many physicians are using azathioprine or infliximab as single therapy, not in combination. Nikita was given both at the sametime.
HEPATOSPLENIC T-CELL LYMPHOMAS Rare postmarketing cases of hepatosplenic T-cell lymphoma have been reported in adolescent and young adult patients with Crohn’s disease treated with REMICADE. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. All of these hepatosplenic T-cell lymphomas with REMICADE have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine.
Other safety issues, such as the risk of malignancy or lymphoma, are still under investigation to better understand the relationship between the disease itself, the treatment and the adverse outcome.
Leukemia occurred after 6 and haly years of infliximab therapy, consistent with a cumulative effect on bone marrow precursor cells.
Patients who develop symptoms of infection should be aggressively treated and considered for hospitalisation, as therapy with infliximab alters the host defence mechanism.
The observations implicate azathioprine as a leukemogenic agent. It will be prudent to review the need for azathioprine therapy when unexpected cytopenias occur and prescription has been prolonged.
Infections can occur because of a shortage of normal white blood cells (a condition called leukopenia) or a shortage of normal neutrophils (called neutropenia). Neutrophils are a type of white blood cell needed to fight infections from bacteria. Patients with AML can get infections that don’t seem to go away or may get one infection after another. Fever often goes along with the infection.
Forty-eight reports of malignancy in children were identified: 31 following infliximab use, 15 following etanercept use, and 2 following adalimumab use. Half of the malignancies reported were lymphomas and included both Hodgkin’s and non-hodgkin’s lymphoma.
In conclusion, therapy with TNF blockers in children may be associated with the development of malignancy. The reported malignancies have occurred in children with JIA and in children with IBD.
Reviewed
White cell count 2.8
Nikita reported while uni she had had urinary tract infection/fever/viral Illness, had attended A&E give Augmentin. Taking Asacol not taking Azathioprine. Nikita reported increase in diarrhoea in November, which was settling. Stool testing for infection was negative, flexible sigmoidoscopy showed mild inflammation, histology consistent with inactive ulcerative colitis with no abnormal growth or development of cell or tissue. Stay on Asacol hold off Azathioprine. Need regular blood tests to monitor her blood count.
Reviewed by Nurse Tracey Tyrell stay off Azathioprine and continue her blood monitoring.
Nikita reported being well last blood results taken at the uni GP practice were reported on 22 March 2011, in light Dr Hart advised to have Azathioprine 50mg once daily. Advised to have an appointment with her GP to repeat her full blood count, liver function tests,CRP in two weeks.
Reviewed Nikita was found to be well and in clinical remission.
Specialist Registrar - In terms of her colitis, she was well. Her bowels were opening once a day with normal motions and without abdominal pains or urgency. It was noted that over the previous three to four days she had experienced some fevers and headaches. Nikita mentioned she had a similar episode a year ago, at which toime she was found to have a urinary infection. No specific symptoms regarding an infection that day, and Dr Peake prescribed antibiotics and advised her to see her GP if she did not improve.
Serious, including fatal, infections are a known risk of TNFα blockers. https://www.remicade.com/shared/product/remicade/prescribing-information.pdf WARNING: SERIOUS INFECTIONS and MALIGNANCY See full prescribing information for complete boxed warning SERIOUS INFECTIONS • Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. • Discontinue REMICADE if a patient develops a serious infection. • Perform test for latent TB; if positive, start treatment for TB prior to starting REMICADE. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. (5.1) MALIGNANCY • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including REMICADE. • Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers including REMICADE. Almost all had received azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of REMICADE cases were reported in patients with Crohn’s disease or ulcerative colitis, most of whom were adolescent or young adult males. (5.2)
Nikita had been to A&E after returning from holiday in Dubai with swollen left leg. Assessed in a&E with no evidence of DVT on scan.It is documented by the IBD nurse that Nikita's mother was advised to contact her GP.
Regarding repeat blood tests. It is noted that Nikita was unwell with tonsillitis and taking penicillin. She was advised to stay off Azathioprine.
Infections can occur because of a shortage of normal white blood cells (a condition called leukopenia) or a shortage of normal neutrophils (called neutropenia). Neutrophils are a type of white blood cell needed to fight infections from bacteria. Patients with AML can get infections that don’t seem to go away or may get one infection after another. Fever often goes along with the infection.
Nikita reported a cold, chesty cough and diarrhoea, and that she was about to see her GP.
Infections can occur because of a shortage of normal white blood cells (a condition called leukopenia) or a shortage of normal neutrophils (called neutropenia). Neutrophils are a type of white blood cell needed to fight infections from bacteria. Patients with AML can get infections that don’t seem to go away or may get one infection after another. Fever often goes along with the infection.
AML risk was reported to be significantly high in ulcerative colitis patients in two studies.36,64
Intensive Care - Giving poor little body a substantial pounding which severely weakened me decreasing the chance of dealing with the upcoming chemotherapy.
Repeated calls from medical team insisted no bone marrow test required.
Family arrange bone marrow test plus others
The cumulative 10-year probability for developing cancer after infliximab was 9%
Awaiting bone marrow results
Bone results back, Nikita nothing to worry about primary or secondary Myelodysplastic syndromes (MDS)
Second bone marrow test nothing to worry about MonoMac, back to University
Second bone marrow test nothing to worry about MonoMac, back to University
Infections can occur because of a shortage of normal white blood cells (a condition called leukopenia) or a shortage of normal neutrophils (called neutropenia). Neutrophils are a type of white blood cell needed to fight infections from bacteria. Patients with AML can get infections that don’t seem to go away or may get one infection after another. Fever often goes along with the infection.
Infections can occur because of a shortage of normal white blood cells (a condition called leukopenia) or a shortage of normal neutrophils (called neutropenia). Neutrophils are a type of white blood cell needed to fight infections from bacteria. Patients with AML can get infections that don’t seem to go away or may get one infection after another. Fever often goes along with the infection.
Diagnosed with Acute myeloid leukemia
Complications transferred for expert treatment
I (a) Bronchopneumonia (b) Acute Myeloid Leukaemia II Ulcerative Colitis
CONCLUSIONS: Risk of T-cell NHL is increased with TNF-α inhibitor use in combination with thiopurines but not with TNF-α inhibitors alone.
WHAT IS CURRENT KNOWLEDGE Risk of lymphomas is higher with the use of TNF- α inhibitors used in combination with thiopurines or thiopurines alone. Hepatosplenic T-cell lymphoma (HSTCL) is a rare but lethal form of T-cell non-Hodgkin ’ s lymphoma (NHL) reported with the use of thiopurines alone and in combination with TNF- α inhibitors. WHAT IS NEW HERE T-cell NHLs are most commonly reported with TNF- α-inhibitor exposure when used in combination with thiopurines. Mycosis fungoides / Sezary syndrome are also commonly reported with TNF- α-inhibitor exposure. Reported risk of T-cell NHL is higher with TNF- α inhibitor used in combination with thiopurines and not when used alone.
Conclusion: These findings suggested that RA patients taking TNF-α antagonist are associated with a lower risk of cancer, but not for hematologic cancers, than RA patients taking nbDMARDs alone.
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