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.

"Real world" outcome of lenalidomide plus dexamethasone in the setting of recurrent and refractory multiple myeloma: extended follow-up of a retrospective multicenter study by the "rete ematologica pugliese".

This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38).

Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections.

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

Evaluation of tumor necrosis factor-alpha and erythropoietin serum levels in B-cell chronic lymphocytic leukemia patients with anemia.

Serum levels of tumor necrosis factor-alpha (TNF-alpha) and of erythropoietin (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic leukemia (CLL) in order to determine whether these factors could be significant in the development of anemia, which was observed in some cases with advanced disease. In our series of patients, TNF-alpha serum levels had an inverse correlation with hemoglobin levels (r = -0.813). In patients with anemia, the serum levels of TNF-alpha were significantly higher (p = 0.022) than in those without anemia (186.7 +/- 84.7 vs. 39.8 +/- 20.7 pg/ml). Serum Epo levels were also significantly (p = 0.0003) increased in CLL patients with anemia compared to those without (134.1 +/- 225.9 vs. 12.3 +/- 4.8 mU/ml). The ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia in 70% of patients with anemia and inadequate in the remaining 30%. In the latter, the mean serum TNF-alpha level was significantly higher (p = 0.005) than the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data suggest that although CLL anemia is not characterized by inadequate Epo production, in some CLL patients this factor may be correlated. In these cases, the levels of TNF-alpha were significantly higher than in other anemic cases. Compared to other CLL patients with anemia, these CLL patients might better respond to therapy with recombinant human Epo in pharmacological doses.

Sensitivity of carbon sequestration costs to soil carbon rates.

Modifying current agricultural management practices as a means of sequestering carbon has been shown to be a relatively low cost way to offset greenhouse gas emissions. In this paper we examine the sensitivity of the estimates of the amount of soil carbon sequestered and the implied costs of sequestering a tonne of carbon to changes in the rates of soil carbon sequestered for alternative production practices. An application is made to the dryland grain production systems of the US Northern Plains where the marginal costs of soil C range from $20 to $100 per MT. We show that the resulting changes in the marginal costs quantities of C sequestered are not a monotonic transformation of the changes in the soil carbon rates. These results underscore the importance of using a linked economic and biophysical simulation model to assess the economic potential for sequestering carbon in agricultural soils.

Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy.

BACKGROUND AND OBJECTIVES: Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively. DESIGN AND METHODS: On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. RESULTS: Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy. INTERPRETATION AND CONCLUSIONS: From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.

Increased risk of lymphoproliferative disorders in relatives of patients with B-cell chronic lymphocytic leukemia: relevance of the degree of familial linkage.

We assessed the familial aggregation of chronic lymphoproliferative diseases (CLD) in 3962 relatives of 169 patients with B-cell chronic lymphocytic leukemia (B-CLL). Data collection included a self-administered questionnaire. The "relative risk" considered the connection between a higher incidence of CLD and the degree of familial linkage with the probands. The model of logistic regression was statistically significant (p < 0.001), with the probability of CLD increasing in proportion to the relationship coefficient between parents, siblings and children [(relationship coefficient 0.5; probability of CLD 1.85 (C.I. 95%, range 1.1-3%)]. CLD, particularly B-CLL, were observed in first-degree relatives of the patients with B-CLL more often than in other relatives.

Community decision-making about critical access hospitals: lessons learned from Montana's Medical Assistance Facility Program.

Limited-service hospitals have been used as a means of maintaining health care services in rural communities with full-service hospitals at risk of closure. The Medical Assistance Facility (MAF) limited-service hospital model has been implemented in 12 communities in Montana and has been evaluated by the Health Care Financing Administration as a viable alternative to a full-service hospital in frontier communities. The 1997 federal Critical Access Hospital (CAH) legislation is the most recent nationwide alternative for maintaining health care in rural communities, and it incorporates many of the features of the MAF model. The purpose of this study was to examine rural community decision making regarding MAF conversion from the perspectives of key informants who were involved in the decision-making process. A descriptive multiple case study design was used. Data were obtained through interviews with community members during site visits. The research focused on identification of local issues that were influential in the decision to convert to or reopen as an MAF, features of the MAF model that made it a locally acceptable alternative, and elements that characterized the decision-making process. The issues found to be influential in the conversion decision and the features that made the MAF locally acceptable were those that made the provision of basic services more stable and sustainable. The study suggests that programs to maintain health care services in isolated communities should allow for and encourage an expanded role for nonphysician providers. The lessons learned from the communities included in this study are instructive to rural communities nationwide that are considering a CAH as well as to policy-makers, researchers, and regional and national health care decision makers.

Evaluation of trisomy 12 by fluorescence in situ hybridization in peripheral blood, bone marrow and lymph nodes of patients with B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVE: Trisomy 12 is the most common numerical chromosomal aberration in patients with B-cell chronic lymphocytic leukemia (B-CLL). Fluorescence in situ hybridization (FISH) has improved the detection of this cytogenetic abnormality and has made detection possible in all phases of the cell cycle. The presence of the trisomy 12 positive (+12) cell population has generally been investigated in leukemic cells obtained from the peripheral blood of CLL patients. To ascertain whether trisomy 12 is expressed homogeneously in cells of different hemopoietic tissues, we applied FISH to lymph node, peripheral blood and bone marrow samples obtained simultaneously from 23 untreated B-CLL patients. DESIGN AND METHODS: Twenty-three newly diagnosed patients with B-CLL, 15 in stage B and 8 in stage C, were included in the present study. Peripheral blood smears, bone marrow aspirate smears and lymph node touch imprints were collected from each patient at diagnosis. Cytologic preparations were examined by light microscopy in order to assess the lymphocyte morphology. Immunophenotyping was performed by cytofluorimetric analysis of the peripheral blood, bone marrow and lymph node mononuclear cell suspensions. The diagnosis was supported in all cases by histologic findings in bone marrow biopsy and lymph node biopsy specimens. Fluorescence in situ hybridization was performed on smears of blood and aspirated bone-marrow and lymph node touch imprints obtained by fresh tissue apposition. RESULTS: In 6 of the 23 cases (26%) trisomy 12 was clearly present in all tissues examined. A comparative analysis of the three different hemopoietic tissues was performed. A higher percentage of leukemic CD5+CD23+ cells was detected in lymph nodes than in peripheral blood and bone marrow. A significantly higher proportion of trisomic cells was observed in lymph nodes samples than in peripheral blood or bone marrow smears of trisomy 12 positive CLL patients. INTERPRETATION AND CONCLUSIONS: Several previous reports show that only a proportion of malignant B-CLL cells carry trisomy 12 when analyzed by interphase FISH. The higher proportion of +12 cells in lymph nodes than in peripheral blood or bone marrow of CLL patients with trisomy 12 could reflect different cell distributions in different tissues, or lymph node specific tropism, or proliferative advantage in selected tissue. At present, the role of trisomy 12 in the pathogenesis of lymphoproliferative disorders is unclear.

Cytophagocytosis by the blast cells in acute myeloid leukemia.

The occurrence of cytophagocytosis as spontaneous ingestion of cells by blast cells has been poorly investigated in acute leukemia. Cytophagocytosis by blasts in acute myeloid leukemia (AML) was observed in eleven patients who represent 1% of AML cases seen in our institution (one M1, two M2, four M4 and four M5). Prominent features of cytophagocytosis by AML blasts are particularly evident in leukemias involving monocytic cells and were more obvious in the bone marrow than the peripheral blood. AML of the monocytic type with cytophagocytosis are frequently associated with cytogenetic aberrations involving chromosomes 8 and 16. Finally the poor outcome of AML patients with cytophagocytosis and their poor response to therapy and short survival is stressed.

Reciprocal translocation t(12;13)(p13;q14) in acute nonlymphoblastic leukemia: report and cytogenetic analysis of two cases.

Two cases of acute nonlymphoblastic leukemia with a reciprocal translocation t(12;13)(p13;q14) are described. Both patients were male adults with a diagnosis of M0 FAB type. Beside standard cytogenetic analysis, we applied fluorescence in situ hybridization (FISH) in order to investigate the position of the RB gene with respect to the breakpoint at 13q14. Our results showed that the RB gene was proximal to the breakpoint, but, apparently, not split in either case.

Constitutive expression of IL-1 beta, M-CSF and c-fms during the myeloid blastic phase of chronic myelogenous leukaemia.

During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non-random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML-BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL-1 beta gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL-1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M-CSF gene and many of the same patients often had a simultaneous co-expression of the proto-oncogene c-fms which encodes for the M-CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M-CSF protein was documented in three of five patients studied. No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.

Mitoxantrone and continuous infusion of cytosine arabinoside in refractory and relapsed acute lymphoblastic leukemia.

Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR.

[Computerized tomography in the staging and the follow-up of Hodgkin's lymphoma of the thorax]. / La tomografia computerizzata nello staging e nel follow-up dei linfomi di Hodgkin a localizzazione toracica.

As yet, the role of Computed Tomography (CT) as a routine imaging technique in the staging and follow-up of thoracic Hodgkin's disease has not been assessed. The authors report the results obtained in 120 patients affected with thoracic Hodgkin's disease, staged and followed by means of chest X-rays and CT. CT better identified intrathoracic involvement of mediastinal nodes, of lung parenchyma, of pleura, and of pericardial and chest walls in 54/120 patients (45%), with staging modifications in 18 (15%) of them only. Treatment was changed only in 12 patients (10%) where radiation therapy had been planned. The clinical value of the additional information yielded by CT was especially evident in the follow-up: CT allowed the correct evaluation of persistent/recurrent disease in 51/117 patients (43.5%), a figure high enough to suggest the use of CT in the routine follow-up of patients affected with thoracic Hodgkin's disease.

Continuous infusion chemotherapy with epirubicin and vincristine in relapsed and refractory acute leukemia.

Twenty-three patients admitted for treatment of refractory or relapsed acute leukemias (12 acute nonlymphocytic leukemias, 4 acute lymphocytic leukemias, 1 acute undifferentiated leukemia, 6 chronic myeloid leukemias in blast crisis) received a regimen employing a 4-day continuous intravenous infusion of epirubicin followed by a 4-day continuous infusion of vincristine. The remission rate (complete and partial) was 52%. This treatment was associated with minimal extrahematologic toxicity, particularly cardiac and gastrointestinal toxicity. This method of administration should be considered a reasonable therapeutic approach to pretreated acute leukemia patients, particularly in elderly patients wishing to avoid chemotherapy-related side effects.