a 24yearold male presented with 2  weeks of abdominal pain , fever , weakness , and palpable splenomegaly .
his complete blood count showed a white cell count of 20,000/cmm , hemoglobin of 6.8  g / dl , and platelet count of 42,000/cmm .
further testing showed prolonged pt and ptt , low haptoglobin , and a very high ddimer suggesting disseminated intravascular coagulation ( dic ) .
a bone marrow biopsy was performed ( figs  1 , 2 , 3 , 4 , 5 , 6 ) .
the t cells were predominantly atypical t cells , with a composite immunophenotype of cd3 and cd45 being brightly positive , tia1 + , tcr + , cd4 , cd8 + ( minority , dim ) , cd56 + ( minority , dim ) , granzyme b on flow cytometry .
testing for epstein barr virus ( ebv ) and terminal deoxynucleotidyl transferase ( tdt ) were negative .
this confirmed a diagnosis of hepatosplenic gamma delta tcell leukemia / lymphoma . computed tomography ( ct ) abdomen ( fig . 
induction chemotherapy was initiated with hyperfractionated cvad ( cyclophosphamide , vincristine , adriamycin , and dexamethasone)/(1a ) alternating with highdose methotrexate ( mtx ) and cytarabine ( arac)/(1b ) .
intrathecal cytarabine ( it arac ) prophylaxis was also started . a restaging bone marrow biopsy after cycles 1a/1b showed residual disease .
hence chemotherapy was changed to a secondline regimen comprising ifosfamide , carboplatin , and etoposide ( ice ) .
a restaging ct scan of the abdomen after cycle 1 of ice showed worsening splenomegaly . given poor cytoreduction of his leukemia with chemotherapy , progressive multisystem organ dysfunction and worsening performance status he was considered transplant ineligible .
he was eventually enrolled in hospice about 6  months from the time of diagnosis .
leishman stain of bone marrow aspirate smear shows an intermediate sized cell with scant cytoplasm and blastoid nuclear morphology with nuclear irregularities .
hematoxylin and eosin stain of the clot section shows a hypercellular marrow with some preservation of trilineage hematopoiesis as well as a subtle , diffuse mononuclear infiltrate . 

t cells in the thymus comprise two subtypes based on their surface expression of either  or  tcell receptors ( tcr ) 1 .
the tcr of  t cells , which form the majority , is encoded by alpha and beta genes , whereas the tcr of  t cell is encoded by the gamma and delta genes 2 .
 and  type t cells originate from a common multipotent double negative precursor in the thymus that homes itself there after originating from the bone marrow precursor lymphoid cells 4 .
 t cells on the other hand do not express cd4/cd8 coreceptors , and do not require conventional antigen presentation through mhc expression for their activation 4 .
hepatosplenic gamma delta tcell leukemia / lymphoma is a type of tcell nonhodgkin 's lymphoma that arises from clonal expansion of  t cells which have suffered a derangement of their genetic machinery from unknown reasons .
it has been hypothesized that chronic mhc unrestricted antigenic stimulation of  t cells seen in chronic infection / inflammation may be a causal factor 5 .
this is based on the fact that these occur with a slightly higher incidence in immunosuppressed solid organ transplant recipients and hiv patients where gamma delta t cells are overstimulated by varying antigenic challenges from repetitive infections 5 , 6 .
associations with the use of infliximab , malaria , cytomegalovirus ( cmv ) , and ebv have been reported 6 , 7 , 8 , 9 .
all patients tend to have splenomegaly and bone marrow involvement 11 , 12 . in a case
series of 21 patients , the incidence of liver involvement was 67% , that of at least one b symptom was 80% , and that of lymphadenopathy was 13% 11 .
this condition has a very aggressive clinical course . in a study by falchook et  al . , median duration of complete remission ( cr ) was 8  months with chop like regimens .
patients who achieved a cr had a median os of 13  months compared with 7.5  months in patients who did not achieve a cr 10 .
this disease shows a distinct sinusoidal pattern of infiltration in the splenic red pulp with sparing of the white pulp .
bone marrow morphology is often nonspecific , but is notable for neoplastic cells in the sinusoids in early stages and an interstitial pattern of infiltration in the later stages 10 .
immunohistochemistry ( ihc ) is classically cd3 + , tcr1 + , tia1 + , cd4 , and cd8. tcr rearrangement shows a clonal rearrangement of the  gene of the t cell  a hallmark of this disease 10 , 12 .
after a diagnosis , which is usually made on a bone marrow biopsy and aspiration , we conduct a staging work up that comprises ct scan of the chest , abdomen , and pelvis looking specifically for lymphadenopathy and hepatosplenomegaly .
a lumbar puncture ( lp ) is carried out in all patients for performing a cerebrospinal fluid ( csf ) flow cytometry and cytopathology for involvement of the nervous system .
one prophylactic dose of intrathecal arac is administered at the conclusion of this first lp .
all of our cases undergo a multidisciplinary review at a leukemia tumor board meeting prior to initiating treatment .
our standard firstline therapy is hypercvad alternated with mtx and highdose cytarabine ( arac ) along with intrathecal prophylaxis , to achieve cytoreduction followed by consolidation with allogeneic bone marrow transplant ( allosct ) , if eligible .
we assess response with a restaging marrow after completing the first cycle of hypercvad to help arrive at a decision about continuing the same chemotherapy regimen versus switching to an alternative regimen .
if hypercvad is not possible given a poor performance status of the patient , we use a clinical trial as our standard secondline approach , if one is available . in the absence of a clinical trial
if clinical status is relatively well maintained , then a combination regimen such as ice / dhap / eshap is employed.if clinical status is not favorable , then a single agent approach , such as with romidepsin or pentostatin is considered , unless a poor performance status dictates eligibility for supportive care alone . 
 
if clinical status is relatively well maintained , then a combination regimen such as ice / dhap / eshap is employed . if clinical status is not favorable , then a single agent approach , such as with romidepsin or pentostatin is considered , unless a poor performance status dictates eligibility for supportive care alone .
although alemtuzumab may be employed as a single agent , it may not be tolerated by patients with a poor performance status . during their chemotherapy treatments
, we offer our patients supportive treatment with prophylactic antibiotics , antivirals , and antifungals , judicious transfusion support , and prophylaxis against tumor lysis syndrome .
we routinely involve specialized chemopharmacists and chemonurses to be a part of our support team for the preparation , dosing , and monitoring of chemotherapy .
we also involve an appropriate palliative pain service and hospice support service when the clinical need arises .
t cells in the thymus comprise two subtypes based on their surface expression of either  or  tcell receptors ( tcr ) 1 .
the tcr of  t cells , which form the majority , is encoded by alpha and beta genes , whereas the tcr of  t cell is encoded by the gamma and delta genes 2 .
 and  type t cells originate from a common multipotent double negative precursor in the thymus that homes itself there after originating from the bone marrow precursor lymphoid cells 4 .
 t cells on the other hand do not express cd4/cd8 coreceptors , and do not require conventional antigen presentation through mhc expression for their activation 4 .
hepatosplenic gamma delta tcell leukemia / lymphoma is a type of tcell nonhodgkin 's lymphoma that arises from clonal expansion of  t cells which have suffered a derangement of their genetic machinery from unknown reasons .
it has been hypothesized that chronic mhc unrestricted antigenic stimulation of  t cells seen in chronic infection / inflammation may be a causal factor 5 .
this is based on the fact that these occur with a slightly higher incidence in immunosuppressed solid organ transplant recipients and hiv patients where gamma delta t cells are overstimulated by varying antigenic challenges from repetitive infections 5 , 6 .
associations with the use of infliximab , malaria , cytomegalovirus ( cmv ) , and ebv have been reported 6 , 7 , 8 , 9 .
median age at diagnosis is 34  years 11 . a slight male gender preponderance exists 11 , 12 .
all patients tend to have splenomegaly and bone marrow involvement 11 , 12 . in a case
series of 21 patients , the incidence of liver involvement was 67% , that of at least one b symptom was 80% , and that of lymphadenopathy was 13% 11 .
this condition has a very aggressive clinical course . in a study by falchook et  al . , median duration of complete remission ( cr ) was 8  months with chop like regimens .
patients who achieved a cr had a median os of 13  months compared with 7.5  months in patients who did not achieve a cr 10 .
this disease shows a distinct sinusoidal pattern of infiltration in the splenic red pulp with sparing of the white pulp .
bone marrow morphology is often nonspecific , but is notable for neoplastic cells in the sinusoids in early stages and an interstitial pattern of infiltration in the later stages 10 .
immunohistochemistry ( ihc ) is classically cd3 + , tcr1 + , tia1 + , cd4 , and cd8. tcr rearrangement shows a clonal rearrangement of the  gene of the t cell  a hallmark of this disease 10 , 12 .
after a diagnosis , which is usually made on a bone marrow biopsy and aspiration , we conduct a staging work up that comprises ct scan of the chest , abdomen , and pelvis looking specifically for lymphadenopathy and hepatosplenomegaly .
a lumbar puncture ( lp ) is carried out in all patients for performing a cerebrospinal fluid ( csf ) flow cytometry and cytopathology for involvement of the nervous system .
one prophylactic dose of intrathecal arac is administered at the conclusion of this first lp .
all of our cases undergo a multidisciplinary review at a leukemia tumor board meeting prior to initiating treatment .
our standard firstline therapy is hypercvad alternated with mtx and highdose cytarabine ( arac ) along with intrathecal prophylaxis , to achieve cytoreduction followed by consolidation with allogeneic bone marrow transplant ( allosct ) , if eligible .
we assess response with a restaging marrow after completing the first cycle of hypercvad to help arrive at a decision about continuing the same chemotherapy regimen versus switching to an alternative regimen . if hypercvad is not possible given a poor performance status of the patient , we use a clinical trial as our standard secondline approach , if one is available . in the absence of a clinical trial
if clinical status is relatively well maintained , then a combination regimen such as ice / dhap / eshap is employed.if clinical status is not favorable , then a single agent approach , such as with romidepsin or pentostatin is considered , unless a poor performance status dictates eligibility for supportive care alone . 
 
if clinical status is relatively well maintained , then a combination regimen such as ice / dhap / eshap is employed . if clinical status is not favorable , then a single agent approach , such as with romidepsin or pentostatin is considered , unless a poor performance status dictates eligibility for supportive care alone .
although alemtuzumab may be employed as a single agent , it may not be tolerated by patients with a poor performance status . during their chemotherapy treatments
, we offer our patients supportive treatment with prophylactic antibiotics , antivirals , and antifungals , judicious transfusion support , and prophylaxis against tumor lysis syndrome .
we routinely involve specialized chemopharmacists and chemonurses to be a part of our support team for the preparation , dosing , and monitoring of chemotherapy .
we also involve an appropriate palliative pain service and hospice support service when the clinical need arises .
 key clinical messagea 24yearold male presented with abdominal pain , fever , and palpable splenomegaly . 
 his differential count revealed myelocytes , metamyelocytes , and nucleated red cells . 
 a bone marrow biopsy confirmed a diagnosis of hepatosplenic gamma delta tcell leukemia / lymphoma . 
 we describe here our center 's diagnostic and treatment approach for this rare leukemia . 