Gianna Maria D’Elia

Epidemiology, features and outcome of pain in patients with advanced hematological malignancies followed in a home care program: an Italian survey

We report on epidemiology, features, outcome, and domiciliary management of pain in patients with advanced hematological malignancies followed by an experienced hospital-based home care (HC) team. Out of 469 patients, 244 (52%) experienced a total of 284 pain syndromes. Pain intensity was rated from mild to moderate in 31% and from moderate to severe in 69% of them. The diagnosed pain mechanisms were deep somatic in 56%, superficial somatic in 15%, visceral 14%, mixed 8%, and neuropathic in 7% of pain syndromes, respectively. Incident pain was observed in 38% of all pain syndromes. In every diagnostic group, deep somatic pain was prevalent. Moreover, 85% of visceral pain syndromes were observed in patients affected by non-Hodgkin’s lymphoma (NHL). In addition, out of 284 pain syndromes, 150 (51%) were caused by bone involvement. The most frequent recognized pain provocative mechanisms were bone marrow expansions, osteolysis, lymph node enlargement, and mucositis. In our experience, an approach based on the association of causal therapies and analgesics allows optimal control of most pain syndromes. Therefore, pain is a major problem in patients affected by advanced hematological malignancies, and its management can be effective and feasible when carried out by a skilled HC team.

Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients

Recent data suggest that proper assessment of comorbidities is useful to predict the outcome of MDS patients receiving allogeneic stem cell transplantation. However, the results obtained in this highly selected subset of patients cannot be applied to the whole MDS population. We evaluated the impact of comorbidities in 418 consecutive MDS patients diagnosed at our institute from 1992 to 2005. All patients were classified according to WHO criteria and all received only conservative and supportive treatment. One or more comorbidities were detected in 390 patients (93%) at the time of diagnosis, with a higher incidence in older patients. Cardiac diseases were the most frequent comorbidities (30%) while diabetes and correlated adverse events were the second cause of comorbidity (20%). We applied 3 comorbidity prognostic scores (CCI, HCT-CI and a MDS-CI score proposed by Della Porta et al.). According to CCI score, 253 patients had a score 0, 111 patients had a score 1 and 54 patients had a score >2. According to HCT-CI, 209 patients had a score 0, 105 patients had a score 1 and 106 patients had a score >2. With MDS-CI score, 288 patients had a score 0 and 129 patients had a score >1. We found a significant correlation between survival and stratification according to CCI and MDS-CI scores (p=0.01 and 0.02, respectively), but not according to HCT-CI score. The number of comorbidities as evaluated according to CCI was directly correlated to the development of RBC transfusion-dependency and was associated to a significantly higher risk of death not related to leukemic evolution (HR = 2.12, p ≤ 0.001). Conversely, higher risk of non-leukemic death did not correlate with higher transfusional requirement according to HCT-CI and MDS-CI scores (p = 0.3 and 0.43, respectively). As suggested by Della Porta et al., also in our experience the presence of cardiac, liver, renal, pulmonary diseases and solid tumours was found to independently affect the risk of death in a multivariable Cox regression analysis (p values from <0.01 to 0.004). In conclusion, assessment of comorbidities at diagnosis in MDS patients may improve the ability of therapeutic decisions.

Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: A retrospective cohort study

The occurrence of secondary hypogammaglobulinemia (SH) after chemo-immunotherapy represents a potential side effect in patients with indolent non-Hodgkin lymphomas (iNHL). Few data are available on SH occurring after chemotherapy and/or Rituximab (R). We retrospectively investigated the incidence and the risk factors for SH and infectious complications in patients with iNHL after chemo-immunotherapy. Two hundred and sixty six patients treated between 1993 and 2011 were studied. Patients with a basal hypogammaglobulinemia or a monoclonal component were excluded. The incidence of SH was 2.2×1000 person-years (95% CI 1.6-2.9). Exposure to Fludarabine-based schedules (Fbs)±R was associated with a hazard ratio (HR) of 18.1 (95% CI: 4.3-77.0). Conversely, exposure to CHOP±R or CVP±R was not a risk factor (HR 0.3, 95% CI: 0.1-0.8; HR 0.3, 95% CI: 0.08-1.4, respectively). The role of R was studied comparing cohorts differing only for R; no differences were found comparing R-CHOP/R-CVP versus CHOP/CVP (HR 1.07, 95% CI: 0.38-3.05) and R-Fbs versus Fbs (HR 2.07, 95% CI: 0.62-6.99). Autologous stem cell transplantation (ASCT) is also a risk factor (HR: 5.2, 95% CI 2.1-13.0). SH patients presented a high risk for pneumonia development (HR 7.07 95% CI: 2.68-18.44). We recommend monitoring of serum immunoglobulins in an attempt to reduce the probability of infection after Fbs or ASCT.

Refractory Anaemia with Excess of Blasts in Transformation Re-Evaluated with the WHO Criteria: Identification of Subgroups with Different Survival

One of the major changes suggested by the World Health Organization (WHO) classification with respect to the French-American-British (FAB) proposal for myelodysplastic syndromes (MDS) was to lower the bone marrow (BM) blast count from 30 to 20%, thus eliminating the refractory anaemia with excess of blasts in transformation (RAEB-t) category. However, a general consensus has not been reached, and several authors still retain RAEB-t as an MDS sub-entity. We re-evaluated our series of 74 patients classified as RAEB-t according to the FAB criteria by stratifying them into two subsets: patients with at least 5% peripheral blast (PB) cells but with BM blasts <20% (group I) and patients with BM blastosis between 20 and 30% and PBs <5% (group II). We found differences among the two groups regarding sex, haematological parameters at presentation (white blood cell and neutrophil counts, haemoglobin level) and frequency of infectious episodes during the course of disease. We did not find differences as to the frequency of acute myeloid leukaemia transformation, but a significant difference was evidenced as to survival (9.3 vs. 16 months in group I vs. group II, respectively; p = 0.02). Furthermore, at our institution, we compared the RAEB-t group I patients who, based on >5% PBs, should be included in the RAEB-II category according to the WHO criteria, with a group of 98 patients who were diagnosed as RAEB-II according to the WHO criteria. The findings showed that the aggregation of these two subsets appeared inappropriate, because patients of the two groups showed different clinical features and rates of acute transformation. In conclusion, the RAEB-t entity according to the FAB criteria, although including heterogeneous clinical patient subsets, should more likely be considered as an advanced stage of MDS, rather than a true acute myeloid leukaemia.

5'-Azacitidine for therapy-related myelodysplastic syndromes after non-Hodgkin lymphoma treatment.

Therapy-related myelodysplastic syndromes are possible complications in patients treated for previous hematologic malignancies. Therapeutic strategies in these type of disorders are still not well defined: azacitidine has been recently approved for the treatment of higher risk myelodysplastic syndromes, but few data are published relating possible efficacy in therapy-related dysplastic disorders. We reported here 4 patients treated with azacitidine for therapy related dysplasia after chemotherapy for non-Hodgkin lymphoma.

Current and future therapeutic approaches for the treatment of follicular lymphoma

ABSTRACT Introduction: Recent advances in prognostication as well as management of Follicular Lymphoma (FL) are moving to personalized approach. Areas covered: Prognostic scores as well as consolidated and innovative therapeutic approaches are evaluated according to the various presentation modalities. For asymptomatic, low-tumor burden FL, a ‘watch and wait’ policy is currently the first-choice approach, although possible alternatives are discussed. Early stage FL may be treated with local radiotherapy although the role of minimal residual disease in possible additional agents should be determined. The first line treatment for symptomatic FL is chemo-immunotherapy followed by two years maintenance therapy with anti-CD20 monoclonal antibodies. A deeper knowledge of FL biology has opened new perspectives regarding the timing of therapy and has offered new targets for the development of novel agents that aim to change the therapeutic scenario of FL management. Expert commentary: The introduction of novel agents could question the incurability of FL and change the therapeutic goal from prolonging the complete remission state to eradicating the disease in young/fit patients, as well as improving quality of life in elderly/unfit patients. In the near future, combining new biologic agents and adoptive cell therapies could help in achieving these aims.

Reappraising the timing of transplant for indolent non-Hodgkin lymphomas

ABSTRACT Introduction: Indolent non-Hodgkin lymphomas (iNHL) remain incurable with standard approaches. The timing of autologous stem cell transplant (ASCT) is changing following the introduction of new drugs that can potentially defer the transplant, improved reduced intensity conditioning (RIC) and haploidentical allogeneic SCT (allo-SCT). Areas covered: The most relevant aspects concerning the role of hematopoietic stem cell transplantation in the management of iNHL are discussed. Literature search methodology included examination of PubMed index and meeting presentations. Expert commentary: ASCT is not currently employed as consolidation in first-line, being reserved to patients with refractory/relapsed disease. The curative potential of graft-versus-lymphoma (GVL) after RIC allo-SCT could be particularly beneficial in patients with iNHL relapsing after ASCT. This scenario could be modified in the near future by better definition of high-risk patients at diagnosis, by the improvement of minimal residual disease (MRD) evaluation and by the introduction of new drugs in the therapeutic algorithm.