Giovanna Mansueto

Glutathione S-transferase P1 Genotype and Prognosis in Hodgkin's Lymphoma

Purpose: Glutathione S-transferase P1 (GSTP1) is a member of the GST enzyme superfamily that is important for the detoxification of several cytotoxic drugs and their by-products. A single nucleotide polymorphism results in the substitution of isoleucine (Ile) to valine (Val) at codon 105, causing a metabolically less active variant of the enzyme. We assessed the impact of the GSTP1 codon 105 genotype on treatment outcome in patients with Hodgkins lymphoma. Experimental Design: The Ile105Val polymorphism in the GSTP1 gene was analyzed using a PCR-RFLP technique. Ninety-seven patients with Hodgkins lymphoma were included and associations with patient characteristics and treatment outcome were analyzed. Results: The GSTP1 Ile105Val polymorphism was associated in a dose-dependent fashion with an improved failure-free survival in patients with Hodgkins lymphoma (P = 0.02). The probability of 5-year survival for patients homozygous for the 105Val/105Val GSTP1 genotype was 100%, for heterozygous patients 74% (95% confidence interval, 56-85), and for patients homozygous for the 105Ile/105Ile genotype 43% (95% confidence interval, 23-61). The Cox multivariate analysis showed that GSTP1 codon 105 genotype was an independent prognostic factor. Conclusions: The GSTP1 genotype predicts clinical outcome in patients with Hodgkins lymphoma.

Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: A brief review

Iron overload is a frequent consequence in transfusion-dependent myelodysplastic syndromes (MDSs), which often requires iron chelation therapy (ICT). Interestingly, ICT may sometimes induce a hematologic improvement that leads to significant reduction or complete interruption of blood transfusions. This phenomenon has been recently described in MDS treated with the new oral chelator deferasirox. Here we briefly review the literature about this phenomenon and discuss the possible biological mechanisms underlying hematologic effects of deferasirox in MDS, starting from a new paradigmatic case in whom both hemoglobin level and platelet count improved, inducing transfusion-independence, soon after starting the treatment with deferasirox.

Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study

A prospective, multicenter, randomized trial comparing pamidronate administration (60–90 mg once a month for 1 year) versus simple observation in 177 patients with asymptomatic myeloma was performed to explore whether the administration of this drug reduces the rate of and/or the time to progression to overt, symptomatic disease. No relevant side effects were recorded in pamidronate-treated patients. With a minimum follow-up of 5 years for live patients, there were 56/89 (62.9%) progressions in the pamidronate-treated group and 55/88 (62.5%) within the controls (p = NS). Median time to progression was 46 and 48 months, respectively (p = NS). Overall survival was also similar between the two groups. Skeletal-related events at the time of progression were observed in 40/55 (72.7%) controls, but only in 22/56 (39.2%) pamidronate-treated patients (p = 0.009). In conclusion, the administration of pamidronate in asymptomatic myeloma, while reducing bone involvement at progression, did not decrease the risk of transformation and the time to progression into overt myeloma.

Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas

BACKGROUND Levels of cell-free circulating DNA have been correlated to clinical characteristics and prognosis in patients with cancers of epithelial origin, while there are no data on patients with B-lymphoproliferative diseases. PATIENTS AND METHODS Cell-free DNA levels in the plasma samples of 142 patients with lymphomas [45 with Hodgkins lymphoma (HL), 63 with diffuse large B-cell non-Hodgkins lymphoma (DLBCL), 24 with follicular, and 10 with mantle cell non-Hodgkins lymphoma (NHL)] at diagnosis and of 41 healthy individuals were determined using a quantitative PCR for the beta-globin gene. RESULTS Levels of circulating DNA in patients with HL, DLBCL, and mantle cell NHL were significantly higher than in controls (P < 0.01 for all). Increased levels of plasma DNA were associated with advanced stage disease, presence of B-symptoms, elevated lactate dehydrogenase levels, and age >60 years (P = 0.009; <0.0001; <0.0001; 0.04, respectively). In HL, histological signs of necrosis and grade 2 type of nodular sclerosis were associated with increased plasma DNA. Elevated plasma DNA levels were associated with an inferior failure-free survival in patients with HL (P = 0.01) and DLBCL (P = 0.03). CONCLUSION Quantification of circulating DNA by real-time PCR at diagnosis can identify patients with elevated levels that are associated with disease characteristics indicating aggressive disease and poor prognosis.

Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party

BACKGROUND The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.

High rate of remissions in chronic myelomonocytic leukemia treated with 5-azacytidine: results of an Italian retrospective study

1 Istituto di Ematologia, Universit à Cattolica del Sacro Cuore, Roma, Italy, 2 Dipartimento di Biotecnologie Cellulari ed Ematologia, Universit à La Sapienza, Roma, Italy, 3 Istituto di Ematologia, Fondazione Policlinico Tor Vergata, Roma, Italy, 4 Ematologia, A.O. SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy, 5 Dipartimento di Onco-Hematology, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy, 6 Divisione di Ematologia, Dipartimento di Medicina Traslazionale, Universit à del Piemonte Orientale Amedeo Avogadro, Novara, Italy, 7 S.Orsola-Malpighi University Hospital, Department of Hematology and Oncological Sciences “Ser à gnoli”, Bologna, Italy, 8 Dipartimento di Ematologia, Ospedale Sant ’ Andrea, Universit à La Sapienza, Roma, Italy and 9 Ematologia, AOU Careggi, Universit à di Firenze, Firenze, Italy

F-18 FDG PET/CT quantization parameters as predictors of outcome in patients with diffuse large B-cell lymphoma

We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained by F‐18 FDG PET/CT (PET/CT) in patients with diffuse large B‐cell Lymphomas (DLBCL) presenting intermediate IPI score.

Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia.

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A shorter time to the first treatment may be predicted by the absolute number of regulatory T-cells in patients with Rai stage 0 chronic lymphocytic leukemia†

Regulatory T-cells (Tregs) are increased in chronic lymphocytic leukemia(CLL) and correlates with clinical and biological features of active/progressive disease. However, little is known about their ability to predict the time to first treatment (TFT). We evaluated 75 patients with Rai stage 0 CLL, in whom the absolute number of Tregs was determined at diagnosis, and correlated to main clinical and biological features, as well as to the need of receiving any specific therapy during the course of the disease. After a median follow-up of 30 months, 12 patients(16%) required therapy at some time from the diagnosis. Treated patients showed a significant higher number of peripheral white blood cells and B-lymphocytes, platelet count, cases with unmutated immunoglobulin heavy chain status, and high-risk cytogenetic abnormalities,as well as lower hemoglobin values, than patients who did not need therapy. A greater number of circulating Tregs was detected in treated patients (P < 0.001). Multivariate analysis confirmed that the absolute number of Tregs was an independent predictor of TFT in these patients, the best predictive cut-off being 41/mL. These data show that the absolute Tregs cell number is able to identify Rai stage 0 CLL patients at higher risk of requiring therapy.

Characteristics and outcome of therapy-related myeloid neoplasms: Report from the Italian network on secondary leukemias

Therapy‐related myeloid neoplasms (t‐MN) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. We report data on 277 t‐MN patients, recruited between 1999 and 2013 by the Italian Network on Secondary Leukemias (104 retrospectively and 173 prospectively registered). Median age at t‐MN diagnosis was 64 years (range, 21–87). Most frequent primary malignancies (PMs) were lymphoproliferative diseases and breast cancer. One hundred and thirty‐three patients had received chemotherapy (CHT), 43 patients radiotherapy (RT), and 101 patients combined CHT/RT for PM. Median time between cytotoxic treatment and t‐MN was 5.7 years, with t‐MN following RT alone associated with significantly longer latency, compared to CHT or combined CHT/RT (mean, 11.2 vs. 7.1 years, P = 0.0005). The addition of topoisomerase‐II inhibitors to alkylating agents was associated with shorter latency compared to alkylating agents alone (median, 6 vs. 8.4 years, P = 0.02). Median survival was 14.6 months from t‐MN diagnosis, and was significantly longer in patients treated with allogeneic stem cell transplantation. Significant factors for survival at the multivariable analysis included age, adverse karyotype, and degree of anemia. Our data underline the prognostic importance of karyotype and age in t‐MN, similar to de novo acute myeloid leukemia. Treatment approaches should not preclude the use of conventional treatments for younger t‐MN patients, including allogeneic stem cell transplantation as potentially curative approach. Am. J. Hematol. 90:E80–E85, 2015.