chronic myelogenous leukemia ( cml ) is a chronic myeloproliferative disorder which remains in chronic phase for a variable period followed by accelerated phase and later blast crisis .
various drugs have been used in the management of cml and these are busulfan , alpha - interferon , hydroxyurea , and imatinib , the last mentioned , a tyrosine kinase inhibitor . in last three decades , the incidence of human immunodeficiency virus ( hiv ) infection has been on the rise .
the immunodeficiency state makes the patient vulnerable to various infections . with the introduction of anti - retroviral therapy and modern antibiotics , the long - term survival of hiv patients
has certainly improved and now hiv is considered as chronic infection . however , it is also observed that there has been an increase in the incidence of cancers in hiv afflicted patients .
there are few case reports about development of cml in hiv-1 patients in adult and pediatric age groups .
we report a case here , where cml was diagnosed earlier and while the treatment was ongoing , hiv infection was detected .
it was observed that the patient not only responded favorably to hydroxyurea , as far as cml was concerned , but is maintaining good health in the presence of hiv infection .
the first case where both these conditions were coexisting was reported in 1995 . in this patient ,
record a case of congenital hiv infection who had cml for more than 10 years .
this patient was treated with antiretroviral agent , zidovudine for hiv and alpha - interferon for coexisting cml webb studied 10 patients in whom cml and hiv was coexistent .
the response to imatinib and combination anti - retroviral therapy ( cart ) was excellent .
combination of imatinib with highly active retroviral therapy was shown to have a good control of cml and hiv over a period of 69 months . in 1997 ,
complete cytogenetic response was documented with a combination of alpha - interferon and zidovudine in an asymptomatic patient of cml and hiv .
before tyrosine - kinase inhibitors appeared on the scene , hydroxyurea was used extensively for two reasons .
one , the cost of the drug was affordable and secondly it offered good control of cml .
in early 1980s , patients with hiv infection were treated with hydroxyurea alone and later this was combined with didanosine or stavudine as first line therapy .
however , results of monotherapy with hydroxyurea in hiv infection were inferior to that of haart .
in addition peripheral neuropathy was observed in 5.8% when hydroxyurea was used as a single agent .
these patients due to altered immunological status often contracted pulmonary tuberculosis and isoniazid used for treating mycobacterial infection further enhanced the chances of peripheral neuropathy .
a 50-year - old male patient was a known case of diabetes mellitus and was being treated for that since 1989 .
he was ; however , quite irregular with this treatment and his diabetes was often out of control . in november 2005
the fever was low grade and there was no history of hemoptysis , dysuria and hematuria .
routine laboratory investigations showed high white blood cell count which was 59,000/mm , and there were premature leucocytes on peripheral smear .
his diabetes was out of control with fbs level 264 mg / dl and ppbs value 372 mg / dl .
a provisional diagnosis of cml with uncontrolled diabetes mellitus was made and he was further investigated .
he was given hydroxyurea 500 mg 3 times a day and subsequently the doses were titrated with reference to wbc count . during the follow - up that spanned over next several months
for this , he was treated with antibiotics and insulin which controlled the infection promptly . in october 2010
, he complained of occasional fever , cough with slight expectoration and loss of appetite , weakness and weight loss .
he was diagnosed to have pulmonary tuberculosis on the basis of his clinical picture and positive tb elisa test ( igm ) for which he received anti tubercular treatment for next 10 months . in february 2011
the treadmill test was strongly positive for exercise induced coronary insufficiency . as his symptoms and stress test suggested coronary heart disease , he was referred to a cardiac center for further evaluation .
2d - echo was carried out which showed echo - concentric lvh , normal resting systolic function , presence of diastolic dysfunction , no regional wall motion abnormalities , and normal pa pressure .
coronary angiography was done on 1 march 2011 which showed lvef 50% and triple vessel disease .
revascularization was contemplated ; however , his routine investigation showed a positive hiv test ; hence no further interventional treatment was carried out .
cd3 , cd4 and cd8 count results were 2940 cells / mm , 393 cells / mm and 2477 cells / mm respectively .
viral load was tested on 5 november 2011and it showed 43356 hiv-1 rna copies / ml .
he was advised to start anti - retroviral therapy along with imatinib , however , patient declined to take this treatment due to lack of resources .
patient continues to take hydroxyurea regularly and in spite of advanced hiv he has not developed any major complications of hiv or cml during his follow - up period .
its incidence in india is recorded from 6 population based cancer registries and varies from 0.8 to 2.2/100,000 for males and from 0.6 to 1.6/100,000 populations for females .
studies based on hospital patients show a higher incidence which ranges from 40% to 82 % of leukemia cases in adults .
majority of patients ( 90 - 95 % ) present in an initial chronic phase of variable duration ( average-5 - 5 years ) .
when initial treatment is started in chronic phase of cml , approximately 95% of patients achieve complete hematological response .
they are : acquired immunodeficiency syndrome ( aids ) defining cancers which include non - hodgkin lymphoma , invasive cervical cancer and kaposi sarcoma .
this patient of cml with hiv-1 infection shows a different clinical course than either presenting singly .
his cml was diagnosed 7 years ago and so far has not shown any evidence of accelerated phase or blast crisis .
the presence of hiv infection was detected 5 years after the diagnosis of cml and though he has not received triple drug therapy , he remains clinically stable . if imatinib was used for cml , he would also need triple drug anti - retroviral therapy because the tyrosine kinase inhibitor does not have any effect on hiv-1 .
therefore for cml coexistent with hiv-1 infection , hydroxyurea as a single agent seems to be useful at least in this case .
in fact , before the advent of effective anti - retroviral agents , many hiv patients were treated with a combination of hydroxyurea and didanosine as hydroxyurea has a synergistic effect with reverse transcriptase inhibitors such as didanosine .
hydroxyurea significantly enhances the antiretroviral effects of the adenosine analog reverse transcriptase inhibitor dideoxyinosine by reducing intracellular de - oxyadenosine triphosphate concentrations due to inhibition of ribonucleotide reductase enzyme . as newer antiviral agents such as protease inhibitors , integrase inhibitors , entry blockers and other agents from reverse transcriptase class ,
were introduced the use of hydroxyurea in the management of hiv-1 became less and less .
though , it was easily available at a lower cost , severe hematological toxicity and associated neuropathy , hydroxyurea was later omitted from the guidelines for the antiretroviral therapy .
he is taking only one agent , hydroxyurea since the diagnosis of cml and has good performance status in spite of having a very low cd4/cd8 ratio .
he was treated for tubercular infection but did not acquire other opportunistic infections in last several months .
he has significant longer survival without an  ideal  treatment for cml or hiv infection .
it is observed that when a single antiretroviral agent is used in the treatment of hiv-1 infection , drug resistance develops in a short time .
this could probably be the first report of a patient who had cml first and later developed hiv .
this case does not fit in conventional classification of hiv associated cancers . as per this definition ,
patients have retroviral infection first and later due to infections such as hhv8 , eb virus or other unknown viruses and/or mechanisms develop different types of cancer at a later date . at the time of preparing this report
( december 2012 ) the patient was taking hydroxyurea and the cml is fairly well controlled .
his performance status remains at zero ( ecog score ) and he regularly visits for follow - up .
 association of cancer and hiv infection is seen in practice . commonly observed cancer in hiv infected patients are non - hodgkin 's lymphoma , cervical cancer and kaposi sarcoma , coexistent chronic myelogenous leukemia ( cml ) and hiv infection are rare . 
 we report a case where these two diseases were found in a patient and were treated with a single agent hydroxyurea . 
INTRODUCTION
REVIEW OF LITERATURE
CASE REPORT
DISCUSSION