Pretreatment prognostic factors for overall survival in primary resistant acute myeloid leukemia.

AIM: Primary resistant acute myeloid leukemia has a very poor prognosis. We assessed pretreatment parameters for their significance as prognostic factors in the overall survival (OS) of 53 acute myeloid leukemia (AML) patients who had failed to achieve complete remission (CR) after first-line standard-dose remission-induction therapy. RESULTS: During the period January 2005-December 2009, 53 with acute myeloid leukemia received two cycles of the 3+7 protocol as a first-line standard-dose remission-induction therapy (ARA-C, days 1-7 and daunorubicin, days 1-3). The HiDAC (5 patients), MiDAC (7 patients), and FLAG-IDA protocols (3 patients) were given as salvage therapy. None of these patients achieved CR. There were 27 (51%) males and 26 (49%) females (median age, 55 years, range 28-76). The median white blood cell count was 53 (range 0.9 -350)×10(9)/L, platelets 44 (range 3-856×10(9)/l) and bone marrow blasts 67%. HCT-IC comorbidity scores were 3 in two (3.8%) patients, 2 in 11 (20.8%), 1 in 12 (22.6%) and 0 in 16 (30.2%) patients. Median OS was 3.9 months (range 1 -20 months). The hepatomegaly, white blood cell count, ECOG PS, serum level of lactate dehydrogenase, dysplastic changes, coexpression of CD64, CD15, CD11b, comorbidities and disease cytogenetics influenced survival. CONCLUSION: This single-center study evaluated the significance of pretreatment factors, and found that patient age, comorbidities, ECOG performance status, leukocytosis, hepatomegaly, LDH, and the disease cytogenetics were factors which influenced the outcomes of primary resistant patients with acute myeloid leukemia. An understanding of these factors may help to predict OS in cases where CR has not been achieved and may help when making further treatment decisions.

Primary cutaneous large B-cell non-Hodgkin lymphoma in first-degree relatives.

Primary cutaneous non-Hodgkin's lymphoma is a heterogeneous group of lymphoproliferative disorders characterized by indolent course, virtually exclusive skin involvement and the absence of systemic disease. We present two brothers, whose mother died of gastric diffuse large B-cell lymphoma, in whom in a period of 4 years primary cutaneous large B-cell non-Hodgkin lymphoma of the skin of the head was diagnosed. They were treated with immunochemotherapy according to R-CHOP protocol (rituximab and adriblastine, cyclophosphamide, oncovine and prednisone) achieving a complete remission. The possible etiological mechanism of this familial lymphoma occurrence is discussed.

Mixed phenotype acute leukemia of T/myeloid type with a prominent cellular heterogeneity and unique karyotypic aberration 45,XY, dic(11;17).

INTRODUCTION: A 26-yr-old male patient with mixed phenotype acute leukemia of T/myeloid type with prominent leukemic cell heterogeneity, and the presence of a so far unreported karyotype aberration in this type of acute leukemia 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) is presented. METHODS: Flow immunocytometry was performed by direct multicolor immunofluorescent technique on bone marrow aspirates. Cytogenetic analyses were performed using G-banding method by direct preparation of unstimulated bone marrow cells and following 24 hours of culture in RPMI 1540 culture medium with 25% fetal calf serum at 37°C RESULTS: The flow immunocytometry of bone marrow nucleated cells revealed the existance of three distinct blast cell populations with overlapping immunophenotypes. Predominant blast cell population had an early myeloid phenotype and aberrant expression of CD7 antigen (HLA-DR(+), CD34(+), anti-MPO(+), CD117(+), CD33(+), CD13(+), CD7(+low), cyCD3(-), TdT(-)). The other two blast cell populations, smaller in cell diameter and less sizable in cell proportion, both shared the T-lymphoid features. The patient was treated with ADE protocol (etoposide, cytarabine and doxorubicine). A complete remission was achieved and lasted 5 months. CONCLUSION: A case of MPAL with complex biological features, 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) karyotype and an aggressive, therapy-resistant clinical course, is presented.

Central nervous system relapse in CD56+, FLT3/ITD+ promyelocytic leukemia.

Central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare and tends to be seen mostly following treatment with all-trans retinoic acid (ATRA), due to prolonged patient survival and poor penetration of the drug in the CNS. At least 10% of extramedullary relapses in APL involve the CNS, and associated factors include an increased age, the BCR isoform, the development of differentiation syndrome, a high white cell count at presentation and hemorrhage into the CNS during induction therapy. We present the case of a patient with high-risk APL, CD56+, CD2+ in whom a CNS relapse was diagnosed through the presence of a PML/RARα rearrangement on PCR of the cerebrospinal fluid (CSF).

Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide.

We retrospectively studied four cases of t-MDS/AML among 210 (1.9%) consecutive patients with CLL treated at a single center with fludarabine and cyclophosphamide (FC) either as the first- or second-line therapy. The median follow-up of the whole cohort of patients was 46months (range: 7-60). Two of these patients (2/130, 1.7%) had been treated with FC only, and two more (2/80, 2.3%) with CHOP and CHOP+FND, respectively, prior to FC. The median age was 61.5years (range: 49-71); three were male. They developed t-MDS/AML after a median latency period of 41months (range: 7-56) from the FC completion. Chromosomal aberrations with an adverse prognostic impact were present in the karyotype of all four patients, including abnormalities of chromosome 5 in three of them, and a rare chromosomal translocation in one patient. Median survival after t-MDS/AML diagnosis was 4months (range: 2-8). Although the agents administered prior to FC make it difficult to assess the risk of t-MDS/AML attributable to FC, this report might be a valuable addition to the literature.

Mycophenolate mophetil therapy for chronic immune thrombocytopenic purpura resistant to steroids, immunosuppressants, and/or splenectomy in adults.

Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5-2 g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14-64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8 × 10(9)/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3-8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p<0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p>0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9-20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at "safe" levels (median 30 × 10(9)/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.

Specific skin lesions in hairy cell leukemia at presentation: case report and review of literature.

Skin involvement in hairy cell leukemia (HCL) at presentation is a relatively rare manifestation of the disease. A 60-year-old male patient in whom cutaneous lesions were the initial manifestation of hairy cell leukemia together with leukocytosis, monocytopenia, massive splenomegaly, and leukemic maculopapulous infiltration of the almost whole skin is described. The present case is the forth mentioned in the literature with specify of leukocytosis in peripheral blood, consisting mostly of hairy cells. The patient was treated with two courses of 2-chlorodeoxiadenosine (2-CdA, Cladribine) and splenectomy and after this cutaneous lesion disappeared and general condition is improved.

Antiribosomal-P protein antibodies in a patient with systemic lupus erythematosus and non-Hodgkin's lymphoma: more than coincidental finding?

Patients with systemic lupus erythematosus (SLE) are at an increased risk of lymphomas, but mechanisms underlying this association are obscure. Recently, it has been shown that antiribosomal-P protein (anti-P) antibodies cross-react with phospholipids and enhance the production of cytokines which may influence lymphomagenesis. We report a 46-year-old woman who suffered high grade diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) 28 months after the diagnosis of SLE. Development of lymphoma was associated with occurrence of serum monoclonal IgM, and pronounced prolongation of phospholipid-dependent clotting tests. Anti-P IgG antibodies were highly positive both on HEp-2 cells and in ELISA test. Anticardiolipin, anti-beta2 glycoprotein I, and antiprothrombin IgM antibodies have also been found in high concentrations. Complete remission of DLBCL and SLE, with normalisation of clotting tests, and disappearance of M component was achieved with administration of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. The progression of SLE to DLBCL associated with presence of anti-P antibodies has not been previously reported. This association may not be coincidental, but further investigations are required to confirm this hypothesis.

Malignant histiocytosis with central nervous system involvement and hepatic mucinous cystadenoma in a single patient with review of the literature.

Malignant histiocytosis is a rare neoplasm of the reticuloendothelial system characterized by neoplastic proliferation of tissue histiocytes. We report a case of malignant histiocytosis in a 64-year-old female initially operated on for a mucinous cystadenoma of her liver. Four months after the operation, skin induration on the neck and anterior thoracic wall and systemic lymphadenopathy were noted. Histology and immunohistochemistry of the lymph node and bone marrow specimens showed extensive infiltration with atypical cells, resembling malignant histiocytes (CD45, CD45RO, CD11c, CD68, lysozyme, antitrypsin and alpha1-antichymotrypsin positive; CD1, CD35, B-cell and T-cells markers negative). She was treated with vinblastine, methotrexate and dexamethasone (3 cycles) without response. The therapy was switched to CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) with disappearance of lymphadenopathy. Bone marrow infiltration by histiocytes was reduced to 20%. Two months after completion of 8 cycles of CHOP she experienced severe headaches, vomiting, loss of consciousness, and developed paraparesis. A CT scan of the brain was normal but the cerebrospinal fluid cytology showed presence of histiocytes. The patient was then treated with intrathecal methotrexate, prednisolone and cytosine-arabinoside and systemic chemotherapy with etoposide and cyclophosphamide. Her condition improved, she became conscious, her headache diminished, she became mobile but skin and nodal lesions reappeared along with extensive marrow histiocytic infiltration. She finally died 22 months after diagnosis.

Primary extranodal lymphomas of gastrointestinal localizations: a single institution 5-yr experience.

This study is aimed at comparison of patients with extranodal lymphomas based on pathohistological findings differences (MALT vs non-MALT) as well as regarding gastric and non-gastric localization, and determining the significance of clinical-laboratory parameters with respect to therapeutic response and length of survival. A total of 56 patients with extranodal non-Hodgkin's lymphomas of the gastrointestinal tract were evaluated over a 5-yr period. Regarding the localization of the disease, the stomach was most frequently affected, 39 patients (70%); followed by small and large intestines, 17 patients. As for the pathohistological findings, MALT lymphoma accounted for 70%, DLBCL 25%, while other subtypes accounted for 5%. Patients' distribution was analyzed according to CS based on both Ann Arbor and Lugano systems; however, the difference obtained between the groups was not statistically significant in both staging types of patients. Statistically significant difference in patients' distribution was not found with respect to IPI index, bone marrow infiltration, anemia, hypoalbuminemia, or histological subtype and localization. Difference in survival between patients according to the pathohistological type was not statistically significant also according to the type of the affected gastrointestinal tract organ. Statistical significance of difference according to survival probability was obtained based on age (survival is longer in patients over 55 yr of age); according to CS and according to Ann Arbor and Lugano classifications (the patients with lower CS live significantly longer); according to IPI index (the survival is significantly longer in patients with lower probability: IPI-0,1, and 2), as well as patients free of bone marrow infiltration whose survival is also significantly longer.

Left-sided gallbladder associated with congenital liver cyst.

BACKGROUND: A left-sided gallbladder is a rare congenital anomaly defined as a gallbladder attached to the lower surface of the left lateral segment of the liver, i.e. to the left of the interlobar fissure and round ligament. CASE OUTLINES: In two women aged 42 and 70 years a left-sided gallbladder was associated with a congenital cyst of the liver. In the first patient, the ectopic gallbladder was an incidental finding at operation for a symptomatic liver cyst; as the gallbladder was normal it was not removed. The second patient underwent operation for chronic calculous cholecystitis, when the left-sided gallbladder and congenital liver cyst were found. An operative cholangiogram was normal, the cystic duct joining the common bile duct from the right side. The gallbladder was removed, and the cyst was de-roofed. Both patients had an uneventful recovery and remain symptom-free at 12 and 9 years respectively. DISCUSSION: To the best of our knowledge, the association of these two congenital anomalies has not been described previously.

Granulocytic sarcoma of the brain in a patient with acute myeloid leukemia.

Granulocytic sarcoma is extramedullary tumor composed of immature leukemic cells most frequently located in close proximity to bone, but it also can be found in the skin, breast, gastrointestinal tract, ovaries and brain. Granulocytic sarcoma may arise during the course of leukemia or precede its development in the bone marrow. The majority of reported cases of granulocytic sarcomas in acute myleoid leukemia have chromosome translocation t(8;21). We report a 46-year-old man with acute myeloid leukemia, type M2 involving the marrow and peripheral blood and chromosome t(8;21) who developed granulocytic sarcoma in the brain, as a first manifestation of relapse 6 months after complete remission was achieved. During a neurosurgical operation a cortically located tumour (3.5 x 5 cm) in the brain was partially removed. Histology showed tumor consisted of homogenous infiltrate of blasts, admixted with more mature haematopoietic cells. The blasts have large round to oval nuclei, delicate chromatin, one or more small well-defined nucleoli and scant basophilic cytoplasm. Immunohistochemistry showed that blast cells were myeloperoxidase positive, confirming the diagnosis of myeloblastic sarcoma in the brain. The patient died two days after surgery.

Neutropenic enterocolitis in acute myeloid leukemia.

In this report we focus on the importance of an accurate diagnosis of gastrointestinal complications during chemotherapy for acute myeloid leukemia. The leukemic infiltrtion of the digestive system may cause mucosal ulcers which can lead to bleeding or perforation. The immune system deficiency in this cohort of patients may result in necrotic enterocolitis (leukemic typhlitis), perianal inflammation, abscesses, and peritonitis. We describe a 37-year old male who presented in June 2004 with 2-month history of fever, weakness and sore throat, treated with antibiotic therapy. Physical examination demonstrated palor. The peripheral blood count at admittance was as follow: Hemoglobin 87 g/l, WBC 63 x 10(9)/l, and platelets 56 x 10(9)/l. The peripheral blood differential count showed: myeloblasts 4%, polymorphonuclear neutrophils (PMN) 20%, monocytes 60%, lymphocytes 16%. The diagnosis of acute myeloid leukemia (AML) was confirmed by bone marrow aspirate, which presented an almost total infiltration by monocytoid blasts, AML type M5 according to FAB classification. Immunophenotypic evaluation by flow cytometry showed that the blast cells reacted with antibodies to CD33, CD13, CD14, CD64, CD15, cytogenetics showed normal karyotype. Induction treatment consisting of cytarabine 2 x 200 mg intravenously in push on days 1-8, vepeside 200 mg i.v. on days 1-5, adriblastine 90 mgon days 1,3 and 5. On day 15 of chemotherapy the patient got fever 38.5 degrees C, abdominal pain and diarrhea (10 stools daily). Broad-spectrum antibiotic therapy with ceftriaxone and amikacin was promptly instituted but condition worsened, abdominal pain extended to all abdomen while the fever and diarrhea persisted. Ultrasonography on day 18 documented bowel wall thickness of colic tract, part of duodenum and jejunum. Owing to suspicion of neutropenic enterocolitis, antibiotic therapy intensified with teicoplanin, fluconazole, metronidazole and pipril. Patient was neutropenic and thrombocytopenic, although daily platelet transfusion from a single donor were given. We started with granulocyte colony stimulating factor (G-CSF) 5 g/kg, which was adiminstered for 7 days. After 7 days neutrophil value reached 1 x 10(9)/l, but fever persisted, abdominal distension and diarrhea progressively improved. The fever peristed and central venous catheter was removed on day 30. After removal of the catheter the patient was getting better: the fever disappeared. The blood count showed Hb 91 g/l, WBC 3,4 x 10(9)/l, platelet 114 x 10(9)/l and normal leukocyte differential count. We emphesize the importance of collaboration between the hematologist and the surgeon in monitoring gastrointestinal complications during and after chemotherapy for acute leukemias and value of abdominal ultrasonography evaluation.

Adenomyoma of the common hepatic duct.

BACKGROUND: Adenomyoma occurs most commonly in the fundus of the gallbladder, seldom in other parts of the gallbladder and rarely in the extrahepatic biliary tree, where most lesions are localised to the common bile duct or papilla of Vater. Adenomyoma of the common hepatic duct is extremely rare. To the best of our knowledge, only three cases have been reported so far. CASE OUTLINE: A 51-year-old woman was admitted with a three month history of attacks of right upper abdominal pain, nausea, vomiting and fever. Laboratory data, ultrasonography, ERCP and CT confirmed slight cholestasis and proximal bile duct dilatation due to a tumour within the common hepatic duct. Cholecystectomy was performed with excision of the suprapancreatic common bile duct including the convergence of the hepatic ducts plus lymphadenectomy and Roux-en-Y hepaticojejunostomy. Frozen section histology showed the benign nature of the lesion and a tumour-free resection line. Final histology showed adenomyoma. The patient has remained symptom free for more than 30 months. DISCUSSION: Although adenomyoma is a benign lesion and the surgical strategy has not been established, complete excision with frozen section is recommended to exclude small malignant foci and local recurrence as well as to avoid surgical over-treatment.

Double mucinous cystadenoma of the pancreas associated with thecoma of the ovary.

Cystadenomas of the pancreas are rare single and isolated tumors, usually appearing in young and middle aged women. Thecomas are rare usually unilateral, benign, estradiol, much rarer androgens producing ovarian tumors. We present a 19 year old girl in whom we removed two mucinous cystadenomas of the tail of the pancreas, 7 and 2 cm in diameter as well as a thecoma of the right ovary. As far as we know this combination of tumors have not been reported before.

[The development of anatomy]. / Razvoj anatomije.

Doctors, particularly surgeons, realise the enormous importance of good knowledge of human anatomy today. It was not so in the past when doctors showed little or no interest for human anatomy for centuries. Dissections of the human body, necessary to study human anatomy, were either forbidden or limited to the corpses of criminals on whom capital punishment was carried out. The authors give a chronology of the development of human anatomy until 19. century when dissections of the human body became almost universally regulated with positive legislation. After the "golden age of surgery" began in 1870. surgeons gave an enormous contribution to anatomy.

[Retropancreatic hematoma mimicking a tumor in a female patient with liver amyloidosis]. / Retropankreasni hematom koji je imitirao tumor kod bolesnice s amiloidozom jetre.

Bleeding in patients with amyloidosis is considered as a frequent complication appearing in up to 40% of cases. It may be spontaneous or provoked. Spontaneous bleeding in the skin or in the gastrointestinal tract is the most frequent. Spontaneous bleeding in the retroperitoneum is rare. It may be diffuse, with possible lethal outcome, or localised, causing haematoma, as in our patient. We present a 62-year old woman with a three-month history of spontaneous, subcutaneous bleeding. No laboratory or other findings could explain the cause of bleeding, as the haemostatic tests were within or close to normal limits. US and CT performed for right subcostal pain discovered a tumour attached to the back of the head of pancreas. Due to mild coaugated hyperbilirubinaemia the "tumour" was held to be the cause of patient's difficulties. However, at operation it turned out to be a retropancreatic haematoma, which was removed and drained. Because of conjugated hyperbilirubinaemia cholecystectomy with operative cholangiography (which was normal) were performed. Due to steatotic appearance of the liver a biopsy was performed. Histological examination revealed amyloidosis. The recovery was uneventful and the patient was transferred to hepatology unit for further treatment where she died 3 months later due to gradual deterioration of kidney and heart function. To our knowledge, retroperitoneal haematoma in liver amyloidosis mimicking retropancreatic tumour has not been reported so far.

[A retroperitoneal bronchogenic cyst]. / Bronhogena cista u retroperitoneumu.

Bronchogenic cyst is a rare congenital (developmental) anomaly. It is usually asymptomatic but its enlargement and localization may cause serious symptoms. Exact preoperative diagnosis is rarely established. As a rule, it is established during histological examination of the resected specimen. We present a patient with a subdiaphragmatic retroperitoneal bronchogenic cyst in whom exact diagnosis was documented by histological examination of excised cyst. To our knowledge this is the third such case ever reported.