The hematology journal : the official journal of the European Haematology Association最新文献

We report a 31-year-old female with t(8;21)(q22;q22) acute myeloid leukemia (AML), M2 in the FAB classification. Complete remission was achieved with daunorubicin and cytarabine induction therapy followed by three courses of high-dose cytarabine consolidation. Only 3 months later, the patient relapsed with granulocytic sarcomas (GSs) in her rhinopharynx, external acoustic meatus, and bone marrow. She received focal radiation for the GSs and successfully underwent reinduction chemotherapy. Subsequently, she received a matched related donor peripheral blood stem cell transplantation followed by high-dose chemotherapy and is now in a second remission. We summarized 79 reported cases of t(8;21) AML with GS and reviewed the literature to identify differences in the characteristics of t(8;21) AML with GS between adults and children. To our knowledge, this is the first report of pharyngeal GS in t(8;21) AML, and focal irradiation plus more intensive postinduction therapy during first remission, such as allogeneic-SCT, may be effective in adult t(8;21) AML patients with GS.

We report two new cases with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion. Case 1 presented with polycythaemia vera (PV) and evolved over 4 years to a myeloproliferative disorder (MPD) resembling the 8p11 myeloproliferative syndrome (EMS). Case 2 presented with B-cell lymphoblastic leukaemia (B-ALL). These cases illustrate the clinical heterogeneity observed in patients with FGFR1 rearrangements and suggest that constitutively activated tyrosine kinases may be more widespread in MPDs.

Introduction: High-dose chemotherapy conditioning regimens for autologous stem cell transplantation generally give similar results in multiple myeloma. We compared two regimens: melphalan versus melphalan plus busulphan.

Methods: In all, 30 untreated patients with stage III low-risk multiple myeloma were studied. After induction with three VAD courses and mobilization with cyclophosphamide 7 g/m(2) and recombinant human granulocyte-colony stimulating factor (rHuG-CSF) (10 microg/kg b.w./die), they received melphalan 200 mg/m(2) (arm A) or busulphan 16 mg/kg plus melphalan 100 mg/m(2) (arm B) for conditioning for transplantation. All patients received maintenance therapy with Interferon 3 MU x 3/week.

Results: Time to engraftment after transplantation was similar in both groups. All patients received rHuG-CSF after reinfusion of peripheral stem cells. No differences emerged in transplant-related infective and noninfective complications. There were no transplant-related deaths. A better response was observed in the melphalan plus busulphan regimen (85 versus 75%, P<0.05). The 5-year overall survival with this regimen was 56 versus 49% with melphalan, and the median survival was 126 months versus 108 months for melphalan (P=0.7). The median progression-free survival was 121 months for melphalan plus busulphan versus 97 months for melphalan (P=0.05).

Conclusion: These two conditioning regimens showed similar overall response rate and overall survival, though progression-free survival was better with busulphan plus melphalan.

Fludarabine, a purine nucleoside analog, is currently indicated for the first-line treatment of chronic lymphocytic leukemia and is also licensed for the management of indolent non-Hodgkin's lymphoma (NHL) in countries such as Switzerland and Canada. Clinical evidence from studies in patients with NHL suggests that fludarabine monotherapy is at least as effective, if not better, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first- and second-line treatment of NHL, achieving objective response rates of 31-84%. The combination of fludarabine with other chemotherapeutic agents such as cyclophosphamide or mitoxantrone also provides the clinician with additional useful treatment options in this setting. Objective response rates of 70-100% have been reported with fludarabine-containing combination regimens, often exceeding those reported with CVP. Furthermore, beneficial effects on overall and progression-free survival have been reported with fludarabine or fludarabine-containing combination regimens in a number of studies, including a significant survival benefit with the combination of fludarabine, cyclophosphamide, mitoxantrone and rituximab. While adverse events such as granulocytopenia, neutropenia and anemia and, less frequently, infectious complications have been reported with fludarabine, its adverse event profile generally compares favorably with that of other available treatment options. Available clinical data therefore indicate that fludarabine has an important role to play in the treatment of patients with indolent NHL. Further, studies are warranted to identify the optimal fludarabine regimen for this patient group.

Acute myeloid leukemia (AML) is a disease, which when left untreated, is invariably fatal. The disease is more common in elderly people, who also fare worse than younger patients with AML due to a higher rate of unfavorable prognostic factors, such as poor performance status, multiple comorbidities, reduced tolerance to treatment, 'unfavorable' chromosomal abnormalities and multidrug resistant protein-1 expression. While many patients achieve a complete remission, the rate of relapse is high and prognosis after relapse very poor. Promising results have been published in recent years using fludarabine-containing combination therapy for AML, most commonly fludarabine +cytarabine + granulocyte colony-stimulating factor (G-CSF) [FLAG], FLAG + mitoxantrone (FLANG), or FLAG + idarubicin (FLAG-Ida). Such combinations maximize favorable cytotoxic interactions between cytarabine and G-CSF, and between cytarabine and fludarabine. In small studies, such combinations used as second-line therapy have resulted in complete response (CR) rates of 36-59%. Early retrospective analyses suggested higher CR rates in patients with refractory AML than in those with relapsed AML, but this observation has not been confirmed in recent prospective trials. Fludarabine-containing combinations have also been evaluated as first-line therapy in high-risk patients and resulted in CR rates of 34-70%, with median survival from 7 to 16 months. The current large MRC randomized high-risk study will provide further data on the use of fludarabine-containing regimens in patients with poor prognosis AML. Further studies are investigating the use of fludarabine in combination with other agents, such as gemtuzumab ozogamicin and gemcitabine, in patients with AML.

Although iron is essential for cell replication and survival, an increase of body iron stores has been implicated in the development of cancer. However, while the association between iron overload and hepatocellular carcinoma is well documented, the relationship with nonhepatocellular malignancies remains ill-defined. In this review, we briefly report the present knowledge regarding the association between iron overload and hematologic malignancies.

FLT3: gene alterations (internal tandem duplications - ITDs - and D835 mutations) are thought to be associated with poor-risk acute myeloid leukemia (AML). However, not all studies confirm this association, so it is still a matter of debate. Moreover, their association with other molecular abnormalities is less studied. We have investigated the presence of FLT3-ITD and D835 mutations in AML patients and their correlation with clinical and biological disease characteristics. The presence of ITD was analyzed in diagnostic samples of 176 AML patients and the D835 mutation in 135 of these patients. In all these patients, the presence of four well-known molecular abnormalities were also simultaneously characterized: PML/RARalpha, AML1/ETO, CBFbeta/MYH11 and MLL rearrangements. In all, 41 (23%) patients harbored FLT3 mutations, with 34 (19.3%) of them positive for the ITD, and seven (5%) positive for the D835 mutation. Of the acute promyelocytic leukemia (APL) patients, 16 (27%) showed FLT3 mutations, more frequently in M3 hypogranular cases (62% versus 17%, P=0.001) and cases with the short (bcr3) PML-RARalpha isoform (69%, P=0.002). In contrast, FLT3 was never altered in patients with inv(16), t(8;21) or 11q23 abnormalities. FLT3 mutations were significantly associated with some negative prognostic features at diagnosis (leukocytosis, high blast-cell percentage, and elevated LDH values), but they were not associated with different disease-free or overall survival. Therefore, we confirm a high frequency of FLT3 mutations in APL and in adult AML without recurrent cytogenetic translocations. In addition, they were not found as independent prognostic factors although associated with several adverse features at diagnosis.