Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab).

Background: The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods: Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results: At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion: Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number: NCT01724021 (ClinicalTrials.gov).

Recovering from chronic myeloid leukemia: the patients' perspective seen through the lens of narrative medicine.

PURPOSE: The main objective of this study is to gain a deeper understanding of how patients suffering from chronic myeloid leukemia (CML) cope with their illness. The study aims to reconstruct the subjective meaning-making process related to CML in order to gain insights into the impact the disease has on patients' emotions and everyday lives, as well as to explore the psychological impact of their being presented with the chance to suspend their therapy and recover from the disease. METHODS: Data were gathered from a qualitative study conducted in Italy on 158 Italian CML patients. Basing the study on the narrative inquiry approach, the patients were required to describe their patient journey in a qualitative narrative diary. These contained prompts to elicit the free expression of their needs, expectations, and priorities. A lexicographic analysis was carried out with T-LAB software and in particular a thematic analysis of elementary contexts (TAECs) and a word association analysis (WAA). RESULTS: The TAEC detected four thematic clusters related to two factors (temporal frame and contextual setting) that explained the variance among the narratives. The WAA evidenced a wide variety of emotions, both positive and negative, as patients reacted to the possibility of interrupting their therapy. CONCLUSIONS: A better understanding of patients' experiences can offer insights into promoting the development of more sustainable healthcare services and into therapeutic innovation aimed at improving patients' quality of life and at engaging them more in their treatment. The findings of this study can also help make medical professionals more aware of the patient's burden and help them identify potential interactions and emotional levers to improve clinical relationships.

Consolidation therapy with idarubicin, cisplatin and prednisone (CIP) after P-VABEC regimen in the treatment of intermediate and high grade non-Hodgkin's lymphoma of the elderly.

Aggressive treatments in elderly patients with NHL are often responsible for acute complications and increased mortality. The present study confirms that P-VABEC is able to induce a high CR rate (71%), with an overall response rate of 92%. The 4-year actuarial OS was 45%, and the FFS was 38%. Despite these good results 57% of CRs relapsed in a relatively short time (median 9.5 months; range 2-47). Because of this we decided to evaluate the role of a consolidation schedule (CIP), including idarubicin and cisplatin. The toxicity of P-VABEC/CIP regimen was comparable to that of P-VABEC alone. After a median follow-up of 20 months (range 8-49), 93% of CR patients treated with P-VABEC-CIP were still in complete remission. The 4-year actuarial overall survival was 92%, and the failure-free survival in CR patients was 72%. The difference in OS and FFS between the two groups was statistically significant. These results suggest that a short course of additional therapy is feasible in elderly patients treated with P-VABEC and may increase the OS and FFS, without adding toxicity.

Third generation chemotherapy with P-VABEC for aggressive non-Hodgkin's lymphomas of the elderly.

Between July 1990 and March 1992, 23 elderly patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL) received a combination chemotherapy (P-VABEC: Etoposide, Adriamycin and Cyclophosphamide on days 1, 15, 29, 43, Vincristine and Bleomycin on days 8, 22, 36, 50 and Prednisolone on weeks 1-9). The regimen was administered on an outpatient basis. The median age of the patients was 67 years (range 60-78); 15 were previously untreated, 8 were on second line therapy; 6 patients (44%) had stage IV disease, 19 (83%) B symptoms, 15 (65%) had bulky disease, and (26%) bone marrow involvement. The complete remission (CR) rate was 57%, and the partial remission (PR) rate 43%, with an overall response rate of (100%). No difference in response rate was observed between previously untreated patients and patients treated with P-VABEC as second-line therapy while hematological and clinical toxicity were very mild.

Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome.

This study evaluated the impact of a new epoetin alfa dosing regimen on quality of life (QOL), transfusion requirements, and hemoglobin (Hb) levels in 133 patients with low-risk myelodysplastic syndrome (MDS) and Hb < or =10 g/dl. Epoetin alfa 40,000 IU was given subcutaneously twice weekly; after 4 weeks, the dose could be reduced to 40,000 IU weekly in patients achieving erythroid response. QOL was assessed using the functional assessment of cancer therapy-anemia (FACT-An) questionnaire. FACT-An scores increased on average by 7.5 after 4 weeks and by 8.8 after 8 weeks compared with baseline. FACT-An scores were positively associated with Hb values (r=0.53, P<0.01). The mean FACT-An score increase at week 8 was 10.2 in responders and 5.6 in nonresponders. The overall erythroid response rate at week 8 was 68%: 74% in transfusion-independent patients and 59% in transfusion-dependent patients. Of all responders at week 8, response was maintained in 86% at week 12, 71% at week 16, 65% at week 20, and 54% at week 24. Treatment was generally well tolerated. Our data provide new and encouraging results regarding the benefits of 40,000 IU biweekly induction doses followed by 40,000 IU weekly in improving QOL, correcting anemia, and reducing transfusion requirements in low-risk MDS patients.

Interferon-alpha in the idiopathic hypereosinophilic syndrome: consideration of five cases.

The therapy of the idiopathic hypereosinophilic syndrome (HES) is largely directed at controlling symptoms and preventing organ damage. Universally accepted therapeutic protocols for HES are still lacking. Patients are treated by different drugs and drug doses, and therapy appears to be mostly aimed at treating symptoms. However, in order to prevent organ damage the roles of the variously employed agents need to be clarified. Interferon was reported to be an effective agent in 44 patients, and our evaluation of five new cases suggested that IFN-alpha may be suitable as a first-line therapy.

A new effective treatment for indolent lymphoma: a pilot study with fludarabine, idarubicin and prednisone combination (FLIDA).

The management of indolent lymphomas is still controversial. Intensive therapies may improve remission rate but in association with toxicity. Fludarabine and idarubicin are very active drugs in indolent lymphomas. This pilot trial was designed to evaluate the efficacy of a regimen comprising fludarabine, idarubicin and prednisone (FLIDA) in the treatment of low-grade non-Hodgkin's lymphoma at diagnosis. We have assessed the response of 16 adult patients (median age 57 years, range 45-71 years) treated on an outpatient basis: the overall response rate was 93.8 per cent (CR 43.8 per cent, PR > or = 50 per cent). The toxicity of this regimen was very low, with no relevant hematological and infectious complications.

Alternating chemotherapy regimen (P-VABEC) for intermediate and high-grade non-Hodgkin's lymphoma of the middle aged and elderly.

An intensive third generation regimen (P-VABEC) including adriamycin, etoposide, cyclophosphamide, vincristine, bleomycin and prednisolone was administered to 43 unselected elderly patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 67, 40 per cent were Ann Arbor stage IV, 73 per cent had 'B' symptoms, 55 per cent had bulky disease, 48 per cent had serum lactate dehydrogenase greater than 450 U/l, 85 per cent had serum thymidine-kinase greater than 4 U/l. Thirty patients were previously untreated. The complete remission (CR) rate was 74 per cent, and the partial remission (PR) rate 23 per cent, with an overall response rate of 97 per cent. The regimen was carried out on an outpatient basis in all patients. No death occurred during therapy. The Kaplan-Meier actuarial survival of all patients at 3-years is 47 per cent, and 50 per cent (16/32) of all patients who attained CR remain alive and in remission at a median of 21+ months (range 6+ to 42+). These results confirm that high remission and failure-free survival rates can be achieved also in elderly unselected patients with aggressive NHL treated with curative intent.

Motility of rhG-CSF-induced neutrophils in patients undergoing chemotherapy: evidence for inhibition detected by image analysis.

The motility of circulating neutrophils from seven patients affected by intermediate and high-grade non-Hodgkin's lymphoma was investigated before and after rhG-CSF administration (5 micrograms/kg/d for 5 d subcutaneously) in the course of chemotherapy. Random motility and bacterial lipopolysaccharide-induced chemotaxis were studied by the micropore filter technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer-assisted image processing system, capable of giving several parameters about the kinetics of cell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was found. The kinetics of cell migration showed that the cells maintained the typical gaussian pattern of random motility. On the contrary, neutrophils were found to have lost the typical stimulated migration peak. These findings are consistent with a rhG-CSF-induced impairment of the directional movement, rather than of the ability of moving at random. These effects were found in patients who, in the same experimental conditions, had displayed an enhanced phagocytosis and phagocytosis-associated chemiluminescence along with an enhanced CD32 expression, not due to an aspecific cell manipulation. Two hypotheses may be taken into account: (i) an increased adhesiveness due to a direct or an indirect activity of the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh-GCSF administration can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to investigate the optimum dosage both to correct neutrophil number and preserve neutrophil functional activities.

Recombinant alpha 2a interferon and polycythemia vera: clinical results and biological evaluation by means of Fourier-transform infrared microspectroscopy.

Polycythemia vera (PV) is a chronic myeloproliferative disease. The use of recombinant alpha 2a Interferon (IFN) therapy in this disease is a novel approach. We applied Fourier-transform infrared microspectroscopy (FT-IR-M) to investigate the behavior and therapeutic responsiveness of PV patients treated with IFN. A spectroscopic parameter (A1/A2) was used, corresponding to the ratio of the integrated areas of the bands at 1080 cm-1 and at 1540 cm-1 due to nucleic acids and proteic components, respectively, calculated on the spectra of single megakaryocytes (MKs). In previous studies, we have pointed out that MKs in PV have a surprisingly strong myeloproliferative impulse when compared to MKs from other chronic myeloproliferative diseases. Nine patients out of the 11 studied exhibited a satisfactory responsiveness to the IFN treatment. Ten patients were evaluated by the A1/A2 parameter. In 8 of these, a good agreement was seen between this parameter and the laboratory data commonly used for the assessment of this disease. The infrared parameter, which we propose, proves to be an original, reliable method for the evaluation of recombinant alpha 2a IFN responsiveness in this disease.

Glutathione-S-transferase activity and multidrug resistance phenotype in chronic lymphocytic leukemia: do they have any clinical relevance?

BACKGROUND: Lymphocytes from patients affected by B-cell chronic lymphocytic leukemia (B-CLL) have frequently been shown to be positive for the multidrug resistance (MDR) phenotype. However, this phenotype does not seem to be responsible for the resistance to alkylating agents usually employed in the management of CLL. METHODS: Lymphocytes from 42 patients were evaluated by flow cytometry for P-170 expression and by spectrophotometry for glutathione-S-transferase (GST) activity. RESULTS: Our findings show that GST is not related to any clinical parameter but is increased in treated patients. Conversely, 85% of patients were positive for P-170 and this was related to the percentage of CD5/CD19-positive lymphocytes. CD5/CD19-negative patients were also negative for P-170. MDR was not related to any clinical parameter evaluated nor to GST activity in lymphocytes. CONCLUSIONS: MDR is constitutively expressed in B-cell chronic lymphocytic leukemia and seems to be related to a CD5/CD19 B-CLL phenotype. The increase of GST activity in treated patients is statistically significant (p < 0.005).

Hepatitis C virus infection in patients with non-Hodgkin's lymphoma.

Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus, has been proposed as a possible causative agent of mixed cryoglobulinaemia. This 'benign' lymphoproliferative disorder can switch over to a malignant B-cell non-Hodgkin's lymphoma (NHL). Therefore HCV infection has been investigated in a series of 50 unselected Italian patients with B-cell NHL. Antibodies against HCV were found in 30% of NHL and HCV viraemia in 32% of cases. HCV-related markers were detected in 34% (17/50) of our NHL patients; this prevalence is particularly significant when compared with HCV seropositivity in Hodgkin's lymphoma (3%) and healthy controls (1.3%).