Early clearance of hairy cell leukaemia in the bone marrow after first-line treatment with cladribine predicts a favourable outcome.

First-line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long-lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression-free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine.

[Budd-Chiari syndrome and splanchnic vein thrombosis: masked myeloproliferative neoplasms and JAK2V617F]. / Sindrome di Budd-Chiari e trombosi delle vene splancniche: neoplasie mieloproliferative mascherate e mutazione di JAK2V617F.

The Budd-Chiari Syndrome (BCS) and the splanchnic vein thrombosis are characterized by hepatic venous outflow obstruction, generally due to venous thrombosis. These rare diseases are usually caused by multiple concurrent factors, including acquired and inherited thrombophilias. Since the diagnosis of myeloproliferative neoplasms (MPNs) is often difficult in patients with BCS and splanchnic vein thrombosis because of spleen enlargement, secondary pancytopenia and bleeding disorders, recent observations have included in the diagnostic work-up the analysis of the JAK2 mutation. The revision of several recent reports clarify the importance of the JAK2V617F detection in the diagnostic work-up of the BCS and splanchnic vein thrombosis, allowing the demonstration of masked MPNs among these cases that may benefit, in the near future, of target molecular therapies directed toward the JAK2 mutation.

Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: further evidence for the arbitrary nature of current classification systems.

From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2-8) developed a peripheral monocytosis >1 x 10(9)/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.

Acute myelogenous leukemia in elderly patients not eligible for intensive chemotherapy: the dark side of the moon.

BACKGROUND: Acute Myelogenous Leukemia (AML) is a common disease in people aged>60 years. About 50% of the patients are not eligible for aggressive chemotherapy (CT) and are only managed with conservative approaches. Results in this subset of patients have not been reported so far. PATIENTS AND METHODS: We retrospectively evaluated 244 consecutive elderly AML patients (M/F 143/101, median age 72 years, range 60-90) diagnosed at our institution from January 1989 to December 1998 and not eligible for intensive CT. Eighty-nine patients (36.5%) had evolved from previous myelodysplasia (sAML). Fifty-three out of 192 (26.4%) patients with available bone marrow (BM) analysis had oligoblastic leukaemia (blasts<40% and WBC<15x10(9)/l). RESULTS: Sixty-seven patients (27.5%) were managed with supportive treatment only. One hundred seventy-seven patients (72.5%), in order to control disease, received conservative CT, consisting of Hydroxyurea (HU) (127 patients, 71.7%), Cytarabine and 6-Thioguanine (39 patients, 22%) or low-dose cytarabine (11 patients, 6.3%). Median overall survival was 179 days (1-3278) with 50 patients (20.5%) surviving>12 months. Older age (>75 years), poor WHO PS (>2), lower PLT levels (<50x10(9)/l) and higher absolute peripheral blast count (>5x10(9)/l) showed a negative prognostic impact on survival in multivariate analysis. CONCLUSIONS: Our data outline the great heterogeneity of elderly AML patients not eligible for intensive CT. A simple scoring system including easily evaluable parameters, which could distinguish subjects with different prognosis, is proposed. Moreover, randomized studies in order to establish best conservative approaches are warranted.

Granulocytic sarcoma with breast and skin presentation: a report of a case successfully treated by local radiation and systemic chemotherapy.

Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders, but can also occur without overt hematologic disease, i.e. in patients with a normal bone marrow and no history of acute myelogenous leukemia. This primary extramedullary lesion may indeed represent a diagnostic and therapeutic dilemma for both the hematopathologist and oncologist. We describe a case of GS diagnosed in a nonleukemic patient and review the literature regarding the pathologic features and treatment of this condition.

Acute myeloblastic leukemia secondary to myelodysplasia (MDS-AML): a comparison of remission induction with three drugs versus standard two-drugs induction.

To evaluate the addition of a third drug to standard induction chemotherapy in patients with MDS-AML, 23 patients (males/females 13/10, median age 54.3 years, range 24-74 years, median MDS duration 9.8 months, range 2-39 months) who received a standard 2-drugs induction were compared with 23 patients (males/females 11/12, median age 45.6 months, range 21-60 years, median MDS duration 8.3 months, range 2-29 months) who received an intensified 3-drugs induction with etoposide. CR rate, median CR duration and median OS were similar in both groups (48% vs 56%, 4.8 vs 5.9 months, 6.5 vs 7.0 months respectively). Among responding patients, all but one, who underwent allogeneic bone marrow transplantation, relapsed. In conclusion, addition of a third drug (etoposide) does not seem to significantly improve the poor prognosis of MDS-AML patients.

Out-patient management of acute myeloid leukemia after consolidation chemotherapy. Role of a hematologic emergency unit.

BACKGROUND AND OBJECTIVE: Increasing attention to quality of life and to health care costs has recently induced several cancer centers to change in-patient management into an out-patient setting even during high risk phases of disease. The aim of this prospective study was to evaluate feasibility and safety, as well as clinical characteristics, of out-hospital management of AML patients during their post-consolidation phase. DESIGN AND METHODS: All patients who were treated over a three year period by the three following protocols were included in the study: AML10 EORTC/GIMEMA for patients with AML, except for APL, aged 60 years; AIDA GIMEMA for APL patients. All patients submitted to the AML10 and AML13 protocols and those patients submitted to the AIDA protocol with difficult peripheral vein access had a central venous catheter (CVC) sited. Patients treated as in-patients were discharged at the end of consolidation chemotherapy provided they were in a good clinical condition. They were routinely evaluated on an out-patient basis twice weekly. In the event of any complication they were referred to the Emergency Unit of our Department dedicated to out-patients with hematologic diseases. RESULTS: One hundred and eleven patients with AML were eligible for intensive chemotherapy. After achievement of complete remission they received a total of 133 consolidation courses and in 127 instances they were followed on an out-patient basis during the aplastic phase. There were 69 cases (54%) of rehospitalization, 68 because of fever and only one because of severe anemia. Rehospitalization occurred in 90%,70% and 38% of courses in AML10, AML13 and AIDA protocols, respectively. Only one patient died: the cause of death was a brain hemorrhage. Coagulase negative staphylococci and viridans streptococci were the organisms most frequently isolated from blood. Most coagulase negative staphylococci were isolated in patients submitted to AML10 and AML13 protocols, who had an indwelling CVC. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 75% of the cases and made early discharge possible in 28% of the cases with antibiotic therapy continued in an out-patient setting. Overall, patients were managed out of the hospital for 66% of the period of post-consolidation neutropenia (77%, 48% and 50% of the post-consolidation neutropenia period in patients treated with AIDA, AML10 and AML13 protocols, respectively). INTERPRETATION AND CONCLUSIONS: Thanks to the availability of an emergency unit specifically dedicated to out-patients with hematologic diseases, selected out-hospital management of AML patients during post-consolidation cytopenia is a feasible, well accepted and cost-saving option, and can contribute to lower the risk of developing severe nosocomial infections. The empiric therapy with once-a-day ceftriaxone plus amikacin was effective, with the exception of staphylococcal infections, and made it possible to discharge patients early to continue treatment in an out-patient setting.

Medical education for practice in nonmetropolitan areas.

A study of patient records sampled from the office practices of 28 family practitioners and general surgeons in a 16-county nonmetropolitan area revealed that a sizable percentage of the diagnoses of problems encountered by family practitioners concern conditions the management of which is primarily taught on a residency service other than family practice, internal medicine, or pediatrics. Surgeons, conversely, are seeing a large percentage of patients with conditions the management of which is generally taught on a primary care residency service. Data from office records were augmented by interview responses of 32 family practitioners and general surgeons to questions about the training that family practice and general surgical residents should receive if they are to be well prepared for practice in nonmetropolitan areas.