Anna Tonso

Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases

A retrospective study of 37 patients with haematological malignancy (21 acute myeloid leukaemia, 11 acute lymphoid leukaemia, two lymphoma, two hairy cell leukaemia, one Hodgkins disease) and histologically documented mucormycosis was conducted to evaluate the clinical characteristics and ascertain the factors which influenced the outcome from mycotic infection. Patients were admitted to 18 haematology divisions in tertiary care or university hospitals in Italy between 1987 and 1995.

Fatal haemoptysis in pulmonary filamentous mycosis: An underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature

A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary‐care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis.

Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study

Patients with diffuse large B-cell lymphoma with an intermediate/high or high-risk according to the age-adjusted International Prognostic Index have a dismal prognosis. This clinical trial suggests that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor prognosis. See related perspective article on page 1194. Background We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma. Design and Methods Ninety-four young patients (age, 18–60) with stage III–IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation. Results The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-free survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox’s multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival. Conclusions These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials.

Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n=25; RAEB n=6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrollment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy.

GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors.

To reduce toxicity in elderly patients with acute promyelocytic leukaemia, in 1997 the Gruppo Italiano Malattie Ematologiche Dell’Adulto (GIMEMA) started an amended protocol for patients aged >60 years, with the same induction [all‐trans retinoic acid (ATRA) + idarubicin] as in younger patients, followed by a single consolidation course (idarubicin + cytarabine) and maintenance with intermittent ATRA. Among 60 enrolled patients, 54 (90%) achieved haematological remission and six died during induction. Four additional patients died in complete remission (CR) from haemorrhage (2) and infection (2) prior or during consolidation therapy. Eleven patients relapsed at a median time of 17·5 months from CR. The 5‐year overall survival (OS), disease‐free survival (DFS) and cumulative incidence of relapse (CIR) rates were 76·1%, 64·6% and 27·4%, respectively. Univariate analysis identified a performance score (PS) = 2 as the only significant adverse prognostic factor for both OS (P = 0·017) and DFS (P = 0·0003). Male sex had an unfavourable impact on DFS (P = 0·021) and on CIR (P = 0·019), but not on OS (P = 0·234). In multivariate analysis for DFS, only PS = 2 retained prognostic significance (HR = 4·5, P = 0·0083). In conclusion, the amended GIMEMA protocol is effective, with similar relapse rate and inferior toxicity compared to the original AIDA 0493. However, considering the recent availability of effective new agents, a less aggressive approach should be tested in this setting.

Invasive fungal infection in patients with myelodysplastic syndrome: a report of twelve cases.

In this report we analyse the risk factors, clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed a invasive fungal infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year-period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients from five of the participating centres. The primary localisation of infection was the lung in 10 cases and skin and paranasal sinus in one case each. Ten patients died at the end of the follow up. The death was mainly attributable to IFI progression in nine of them. The factors which appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localisation at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.

Long term outcome of localized aggressive non-Hodgkin lymphoma treated with a short weekly chemotherapy regimen (doxorubicin, cyclophosphamide, bleomycin, vincristine, and prednisone) and involved field radiotherapy: result of a Gruppo Italiano Multiregionale per lo Studio dei Linfomi e Leucenie (GIMURELL) study

Recently, management of limited stage diffuse large cell lymphoma (DLCL) is trending toward a low intensity chemotherapy approach. Since 1993 we have used a brief weekly (6 weeks) chemotherapy scheme (Doxorubicin, Cyclophosphamide, Bleomycin, Vincristine, and Prednisone = ACOP-B) followed by involved field radiotherapy in 207 consecutive patients with well defined localized DLCL without age limit (median 57 years, range 18–85). Treatment was completed as designed in 183 of 207 patients (88%). One hundred and ninety-nine patients (96%) achieved complete remission. At a median follow-up of 66 months 170 patients are alive (82%), 168 of them free of disease. Twenty-nine patients experienced relapse after achieving a complete remission. Kaplan-Meier, risk of relapse was 24% after 13 years. Thirty (14.5%) patients have died, 14 (6.8%) due to lymphoma progression, one due to regimen toxicity and 15 (7.2%) from other causes while remaining in complete remission. The probability of overall survival and event free survival at 13 years was 78% (95% CI 70–87%) and 63% (95% CI 50–75), respectively. Crude rate of secondary malignancy was 5.26 /1000 person-years. The ACOP-B regimen plus involved field radiotherapy is well tolerated both short and long term and is an effective chemotherapy scheme for very well defined limited stage aggressive non-Hodgkin lymphomas in all age categories.

Filamentous Fungi Infection in patients with myelodysplastic syndrome. A report of twelve cases

In this report we analyse the risk factors, the clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed an Invasive Fungi Infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients, from 5 of the participating centres. The primary localization of infection was lung in 10 cases and skin and paranasal sinus in 1 case each. Ten patients died at the end of follow up. The death was mainly attributable to IFI progression in nine of them. The factors that appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localization at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.