chronic myelogenous leukemia ( cml ) is a malignant clonal disorder of hemopoietic stem cells characterized by abnormal proliferation and accumulation of immature granulocytes .
leukostasis is one of the complications of cml and is characterized by partial or total occlusion of microcirculation by aggregation of leukemic cells and thrombi leading to respiratory , ophthalmic or neurologic symptoms .
avascular necrosis of bone occurs in the areas with poor collateral circulation when the only branch supplying blood is unable to fulfill the requirements of the bone .
commonly affected areas are head of the femur , head of the humerus , femoral condyles and tibial plateau .
very few cases dealing with cml and avascular necrosis due to leukostasis have been reported . here ,
we report a rare case of 21 year - old male patient with avascular necrosis of right femoral head owing to leukostasis as the initial presentation of cml .
a 21-year - old male patient was presented with pain in the right hip joint for 2 months .
he was a soldier and went to the dispensary of the unit that he belonged to .
he was referred to our hospital for further evaluation of abnormal complete blood cell count which was performed at the dispensary .
the patient suffered from weight loss , mild dyspnea , fatigue , intermittent fever , and night sweat .
, it was observed that the patient was in poor general condition with pallor skin and anemic conjunctiva .
laboratory investigations revealed leukocytosis with leukocyte count of 96,800/mm , increased platelets with a count of 684,000/mm , and hemoglobin level of 10.4 g / dl .
bone marrow examination revealed that the entire marrow space was packed with granulocytes and megakaryocytes .
the bone marrow aspiration showed 0.4% myeloblasts , 6% promyelocytes , 13.2% myelocytes , 15.2% metamyelocytes , 14.7% band neutrophils , 40% segmented neutrophils , 2.7% eosinophils , 0% basophils , 0.8% monocytes , 0.4% pronormoblasts , 0% lymphoblasts , 0% immature lymphocytes , 0.4% lymphocytes , 0.4% plasma cells , and 0% histiocytes suggesting chronic phase of cml .
chromosomal analysis of bone marrow revealed philadelphia chromosome , t ( 9;22 ) and molecular cytogenetics also showed bcr - abl positive .
treatment with hydroxyurea was induced , combined with immediate evaluation of right hip joint pain .
radiolucency superimposing the right femoral head was seen on the pelvic x - ray ( figure 1 ) .
magnetic resonance imaging ( mri ) of both the hips revealed inhomogenously decreased signal intensity in the both proximal femur and acetabulum on t1 weighted images .
the outer areas surrounding these areas had increased signal densities on t2 weighted images ( figure 2 ) . on application of contrast medium , area with former decreased signal density on the cranial part of the right femoral head and some smaller areas of the left femoral head , showed a lack of signal enhancement .
bilateral joint effusion , worse in the right than the left , was also seen .
the leukocyte count decreased from 96,800/ul to 26,300/mm with the treatment of hydroxyurea ( 3 g / day ) for 2 weeks and subsequently hydroxyurea was replaced with imatinib mesyalte . with this
the size of the spleen decreased to 3 cm below the costal margin within 1 month .
following normalization of the peripheral blood counts , the patient was transferred to the department of orthopedics .
he underwent a bipolar hemiarthoplasty of the right hip joint , because the necrosis of the right hip joint was more severe than the left and he had no pain in the left hip joint .
the postoperative course was complicated due to bleeding from the operative site possibly due to thrombocytopenia which may have been induced by imatinib mesylate .
temporarily , the medication of imatinib mesylate was stopped , and the patient was transfused with platelets and packed red cells .
the biopsy revealed focal subchondral necrotic areas in the right hip joint ( figure 3 ) .
the patient was on a continuous follow up and showed no complications with complete cytogenetic response and has been on medication of imatinib mesylate ( 400 mg / day ) .
cml is characterized by a chronic phase which lasts from months to years , and is followed by accelerated myeloproliferative phase and subsequently blast crisis . in the chronic phase ,
manifestations include anemia , splenomegaly , bleeding , and constitutional symptoms such as fatigue , lethargy , weight loss , or low - grade fever . as in the present case study our case of a 21-year - old male , symptoms secondary to leukostasis may also be the presenting features1 ) .
since there are no reliable clinical criteria , in practice , leukostasis is empirically diagnosed when patients present with leukemia , hyperleukocytosis and respiratoy or neurologic distress2 )
. however , some patients have clinically suspected or pathologically proven leukostasis with leukemic blast counts significantly lower than 100,000/mm3 ) .
litchmann proposed a pathophysiological model of leukostasis , based on the rheological consequences of hyperleukocytosis .
he determined that the viscosity of leukocyte suspensions in vitro increased dramatically when the fractional volume of leukocytes ( also known as leukocrit ) exceeded 12~15 ml / dl4 ) .
the concentration of leukocytes necessary to produce such leukocrits is a function of the mean cell volume ( mcv ) of the cells . since leukemic myeloblasts have larger mcv than leukemic lymphoblasts
, leukostasis is more frequently observed in patients with acute or chronic myelogenous leukemia than in patients with acute or chronic lymphoblastic leukemia5 ) .
however , leukemic blast concentrations necessary to reach leukocrit of 12~15 ml / dl are rarely seen .
therefore , additional factors possibly related to the adhesive or invasive properties of leukemic blasts , may be more important .
there are indications that leukemic blast - endothelial cell interactions may be triggered by locally released chemoattractant factors6 ) .
several adhesion molecules ( cd54 , cd62e , cd62p , cd106 ) are up - regulated in endothelial cell of aml patients with leukocytosis6 ) .
blasts appear to have the ability to secrete cytokines such as tnf- and interleukin-1 and therefore bring about the activation of endothelium .
for instance , activation of vascular endothelium by tumor necrosis factor - alpha ( tnf- ) has been reported to increase the adhesion of myeloid blasts8 ) .
once leukocytosis is developed , signs and symptoms are usually related to the involvement of the respiratory or central nervous system .
additional but less common clinical findings include neck vein distension , gallop rhythm and electrocardiographic sign of right ventricular overload , myocardial ischemia , priapism , acute limb ischemia , bowel infarctions , renal vein thrombosis , sudden bilateral deafness and avascular necrosis of bone2 ) . until now , in cml ,
avascular necrosis of femoral head due to leukostasis has not been adequately documented , probably due to the rarity of its occurrence .
after reviewing the world medical literature , we encountered only few cases of cml associated with avascular necrosis of femoral head9 - 13 ) .
the current standard of care for hyperleukocytosis and leukostasis should be the immediate initiation of intravenous fluids , allopurinol , hydroxyurea and the correction of coagulopathy and thrombocytopenia2 ) . due to paucity of data on the efficacy of leukapheresis in reducing early mortality and/or improving overall survival ,
unfortunately there are no evidences to prove that any of these measures have produced a reduction in the number of early deaths .
a variety of traumatic and nontraumatic factors contribute to the etiology of avacular necrosis . in adult patients , corticosteroid
use and excessive alcohol intake are reported to account for more than 90 percent of cases15 ) .
additionally , other causes of avascular necrosis are systemic lupus erythematus , antiphospholipid antibody , trauma , sickle cell hemoglobinopathes , gaucher 's disease , caisson disease ( dysbarism ) , transplantation , interferon- , inherited thrombophilia , or hiv infection16 - 19 ) .
avascular necrosis usually occurs in the anterolateral femoral head , although it may also affect the humeral head , femoral condyles , proximal tibia , vertebrae , and small bones of the hand and foot20 ) .
many patients have bilateral involvement at the time of diagnosis , including disease of the hips , knees , and shoulders .
the goal of therapy for avascular necrosis is to preserve the naive joint for as long as possible .
 chronic myelogenous leukemia ( cml ) is a malignant clonal disorder of hemopoietic stem cells characterized by abnormal proliferation and accumulation of immature granulocyte . 
 leukostasis is one of the complications of cml and is characterized by partial or total occlusion of microcirculation by aggregation of leukemic cells and thrombi leading to respiratory , ophthalmic or neurologic symptoms . 
 we experienced a rare case of avascular necrosis of the femoral head as the initial presentation of chronic myelogenous leukemia . 
 a 24-year - old male patient was admitted to our hospital with pain in the right hip joint . 
 the patient was diagnosed to be suffering from chronic myelogenous leukemia by packed marrow with granulocytic and megakaryocytic hyperplasia and the presence of philadelphia chromosome . 
 the right hip joint pain was attributed to avascular necrosis of the femoral head . and 
 the avascular necrosis could be considered as the complication of chronic myelogenous leukemia due to microcirculatory obstruction of the femoral head . 
 the avascular necrosis of the right femoral head was treated with bipolar hemiarthoplasty . 
INTRODUCTION
CASE REPORT
DISCUSSION