Massimiliano Palombi

Transfusions at home in patients with myelodysplastic syndromes

We report descriptive data of a home care (HC) program, throughout a 5-years period (2006-2010), focusing on the reliability and the safety of transfusions at home in 211 patients affected by myelodysplastic syndromes (MDS). Our results outline the potentially relevant role of a specifically dedicated HC service in the global management of frail MDS patients for which transfusions at home may represent a valuable option to maintain a good quality of life and avoid the possible discomfort due to hospital admissions and outpatient visits.

Anticoagulant and Anti-thrombotic Treatments in the Management of Hematological Malignancies in a Home Care Program

Aim: Anticoagulants (AC) and anti-platelet (AP) agents are widely administered to patients with hematological malignancies (HM). However, HM patients may be at high risk of bleeding and hemorrhagic complications, because of different form of coagulopathies and several degrees of thrombocytopenia. Materials and Methods: A prospective evaluation of the use of anticoagulant and anti-thrombotic agents as well as of bleeding and thrombotic complications in a consecutive cohort of patients, which were followed during the first semester of 2010 by our home care service, was performed. In this regard, three pharmacological class of agents, such as oral anticoagulants (warfarin and acenocumarine), low molecular weight heparin (LMWH) and anti-platelet (AP) drugs were considered. Results: Out of 129 patients, 26 (20%) were treated with AC/AP drugs. Warfarin, acenocumarine, LMWH as well as AP were used in 7, 11 and 12 patients, respectively. Adverse events (bleeding) were observed in 3 patients (11.5%), 2 cases being on warfarin (replaced by LMWH) and 1 being AP (suspension without replacement); out of the 3 patients with bleeding, none presented thrombocytopenia. Conclusions: Despite the frequent findings of hemostatic disorders in a population of frail patients managed in a home care setting, our experience demonstrated that the use of AC/AP drugs has been very rarely responsible for significant complications.

Long-lasting remission induced by rituximab in two cases of refractory autoimmune haemolytic anaemia due to cold agglutinins

Dear Sir, cold-agglutinin-induced autoimmune haemolytic anaemia (AIHA) can be a therapeutic challenge1, for which rituximab has been used with favourable results2–4. We report on two patients with refractory AIHA due to cold antibodies who were successfully treated with anti-CD20 monoclonal antibody in our institution.

Accidental falls in home care hematological patients

Dear Editor, Accidental falls are a major concern in patients with both medical and surgical illness for twomain reasons: (1) potential complications, such as bone fractures, leading to hospitalization requirement and direct or indirect cost increase; (2) medico-legal and insurance implications of a fall and its complications, above all in controlled environments, such as hospital wards, nursing homes, and home care (HC). HC management is a special area of application in advancedterminal onco-hematological and older hematological patients, which is concerned with several factors, such as difficulty with access to a hospital and obtaining considerable benefits from HC, when compared with inpatient management. HC management allows the assistance of hematological patients at home, furnishing the health services that usually would be supplied in a hospital to treat hematological diseases and their complications (e.g., medical examinations, blood tests, transfusions, chemotherapy, etc.) [1–3]. Hematological patients, due to the underlying disease, their treatment, or associated comorbidities, are faced with several pathological processes, which may increase the risk of accidental falls in comparison to the general population. Risk factors for accidental falls have been extensively analyzed, both in the general population (children [4], elderly [5]) and in certain diseases (dialysis [6], stroke [7], cancer [8]), as well as in various settings (such as hospitals [9] and nursing homes [10]). An extensive literature search was conducted through database scanning, revealing lack of evidence regarding falls and injury in hematological HC patients. HC hematological patients could be considered at high risk both for accidental falls (due to age [8] and clinical features, such as anemia [11], fatigue, disability [12–16], cognitive impairment [17], and drugs [18, 19]), and for subsequent complications, such as fractures (due to osteolysis, treatment-induced/enhanced osteoporosis [20]), bleeding (due to hemostasis disorders), and infection. The aim of the present study was to retrospectively evaluate fall frequency and fall injury in hematological HCmanaged patients. Clinical data of 193 patients admitted in our HC service from January 2010 to June 2011 (median follow-up, 74 days (range, 15–500)) were retrospectively reviewed. Among these, 133 patients, with properly recorded clinical data, were considered evaluable for further analysis; 60 patients were excluded due to incomplete data recording (e.g., lack of registration of physical examination data). Accidental fall events (defined as “unexpected descent to the floor”) were extracted and analyzed, as well as complications and their outcome. Evaluable patient data were the following: 54 males (41 %), 79 females (59 %); diagnosis and disease stage are shown in Table 1. Median age was 83 years (20–98); age range details are shown in Table 2. Twenty-six fall events were identified in 23/133 pts (17 %). A total of 18,886 days A. Tendas : L. Cupelli :M. M. Trawinska : L. Lentini Hematology Unit, S. Eugenio Hospital, Home Care Service of the Rome Section of the Italian Association Against Leukemias (RomAIL), Rome, Italy

Motor disability in the setting of oral anticoagulant therapy.

Oral anticoagulant therapy (OAT) is a widely applied measure for the prevention of thrombotic events in a broad range of diseases. OAT is chronically administered and, given its narrow therapeutic range, its management requires close monitoring of prothrombin time (PT) and the international normalized ratio (INR) to balance the risk of hemorrhage and thrombosis. Although PT/INR can be assessed by healthcare professionals or by patients themselves [1], individuals on OAT are usually followed at an outpatient center specializing in hematology. Patients on OAT are typically older individuals and may be affected by various diseases and comorbidities which may exhibit debilitating deteriorations in personal status, physical impairment, several forms of motor disability (MD), and limitations in performing activities of daily living (ADL), the latter eventually resulting in the loss of independence. Moreover, limitations in performing daily activities can compromise the patient’s quality of life (QoL) and increase the burden on caregivers. Therefore, the need of hospital visits may be problematic, given the complex burden of frailty and disability afflicting many patients on OAT, above all the elderly and those with multiple comorbidities. In this regard, hematologists and other medical specialists providing OAT will increasingly be faced with problems arising from functional decline and physical deterioration. Although these concerns are observed as common complaints in patients on OAT in daily clinical practice, information regarding its origins, frequency, and management is relatively scarce. To address this issue, we conducted a cross-sectional evaluation of the MD in a group of consecutive OAT patients. MD was assessed with the Barthel index (BI) [2], which has been used in our previous studies on physical status and motor impairment in hematological patients. As in these previous reports [3, 4], in the present study BI was used as the basic ADL ability scale, and was classified as mild (BI [ 66%), moderate (BI 33–66%) and severe (BI \ 33%). There were 122 patients (73 male); median age was 71 (27–91) years. Disability was present in 37/122 (30%) patients; of the 37 disabled patients, motor impairment was mild in 33 (90%), moderate in 3 (7%) and severe in 1 (3%) patients, respectively. Analysis of BI items (Fig. 1; Table 1) revealed that bladder function and complex activities are the most frequently impaired basic ADL in patients on OAT. Although preliminary and related to a limited series of patients, our data add to the scarce knowledge on disability in the management of OAT and may stimulate further research on this neglected issue. MD is a frequent feature and larger data analyses are likely to provide a better understanding of the disablement process, onset, causes, related risk factors and progression. Meanwhile, for physically impaired patients on chronic OAT, which are only one-third of the total but represent an important management burden if we consider the entire OAT population, we should develop facilitation strategies. In this view, home care management [5], including the at-home use of a portable PT monitor [1] in selected patients, may be suitable L. Scaramucci A. Tendas P. Niscola (&) M. Giovannini M. Palombi L. Cupelli A. Perrotti P. de Fabritiis Hematology Unit, S. Eugenio Hospital, Rome, Italy e-mail: pasquale.niscola@uniroma2.it

Hodgkin disease subsequent to follicular lymphoma on maintenance rituximab.

In the course of follicular lymphomas (FL), although a disease transformation in clinically more aggressive lymphoproliferative disorders, mostly diffuse large Bcells non-Hodgkin lymphomas (NHL), may develop in a consistent proportion of cases [1], the occurrence of Hodgkin disease (HD) in a FL patient represents a rare event [2]. A 67-year-old male patient was seen in August 2005 because of right cervical lymphadenopathy. The lymph node was removed. The resected tissue revealed closely packed and uniform follicles consisting of a mixture of small size centrocytes and no more than 15 medium-sized or large centroblasts for high power field. Immunoistochemical staining revealed that neoplastic follicles expressed CD20, CD10, bcl-2 and bcl-6; a proliferation index of 25 – 40% as showed by expression of Ki67 was also detected [Figures 1(A) – 1(L)]. Thus, a diagnosis of grade 2 FL was made. A comprehensive work-up revealed intra-abdominal limphadenopathies; bone marrow was not involved. The patient was diagnosed as having a stage IIIA FL and was enrolled in a clinical trial, receiving four cycles of FND (fludarabine, mitoxantrone and dexametazone) regimen by which he achieved a complete response (CR). Therefore, 4 weekly rituximab (375 mg/m) were given as consolidation treatment and then he received the same dose every 2 months as maintenance therapy. In October 2006, the patient, having received the last rituximab dose 2 months before, presented with general malaise, sweating and weight loss. The physical and radiological evaluations showed cervical and para-aortic enlarged lymph nodes. A comprehensive laboratory work-up revealed mild normochromic anaemia and elevated levels of lactic acid dehydrogenase and erythrocyte sedimentation rate. A left cervical lymph node biopsy was performed. The pathological examination of the removed lymph node revealed classic Reed-Sternberg and mononuclear Hodgkin’s cells (HC), which were surrounded by a rosettes of T CD3 positive lymphocytes [Figures 1(M) – 1(R)]. These features were consistent with a diagnosis of lymphocyte – depletion subtype Hodgkin disease. On immunoistochemical staining, HC were CD15 and CD30 positive and showed a weak bcl-2 expression. In the light of the reported high aggressiveness and the poor prognosis portrayed by HD when occurring in the course of lymphoproliferative disorders [3,4], the patient was treated with two cycles of IEV (ifosfamide, epirubicin and etoposide) regimen. Therefore, the achieved CR was then consolidated by an autologous stem cells transplantation (ASCT), which provided clinical and survival benefits have been reported in this setting [5]. To date, 6 months after the ASCT,

Homecare-based motor rehabilitation in musculoskeletal chronic graft versus host disease

Chronic graft versus host disease (cGVHD) is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD) was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

Gelatinous Degeneration of the Bone Marrow: Two Case Reports Showing Different Hematological Features and Clinical Outcomes

patient did not present either spleen or liver enlargement. Full blood count on admission showed normochromicnormocytic anemia with reticulocytopenia and normal white blood cell and platelet counts. Total and unconjugated bilirubin and serum haptoglobin levels were normal. Direct and indirect Coombs tests were negative. Serological tests for human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, parvovirus B19 and B and C hepatitis viruses were negative. In addition, the serum levels of triiodothyronine were normal. Moreover, no clinical or laboratory features of autoimmune diseases were revealed. Examination of peripheral blood smears revealed normal red blood cells, whereas erythrocyte fragments were not detectable. The radiological results, which included a whole-body CT, revealed no abnormalities. An occult blood loss was ruled out by fecal and urine analyses. A BM aspirate performed on admission resulted in a dry tap. Therefore, a BM trephine biopsy was taken. Histological examination of the BM sample revealed GMT ( fig. 1 ). The patient did not respond to treatment, which included erythropoietin, prednisone and cyclosporine. Currently, she is maintained with supportive therapy only, consisting of two units of packed red blood cells every 2 weeks. For the past 22 months, her hematological status has remained stable. Gelatinous bone marrow transformation (GMT) is a rare histological disorder of unknown pathogenesis. It is characterized by fat cell atrophy, focal loss of hematopoietic cells and deposition of extracellular gelatinous substances, which are histochemically mucopolysaccharides, rich in hyaluronic acid [1] . GMT has been reported to occur in association with chronic debilitating diseases such as anorexia nervosa, malnutrition and HIV infection, and following treatment-induced cytotoxicity of the bone marrow (BM) [2, 3] . However, very few cases of GMT have been reported outside the setting of malnutrition and the cancer anorexia-cachexia syndrome. This complication has been described in association with several hematological malignancies, such as myelodysplastic syndrome and acute myeloblastic leukemia [4] with monosomy 7, and with other neoplastic disorders [5] . In this report, we describe 2 cases of GMT that were not associated with any of the previously reported medical conditions and were characterized by different hematological features and clinical outcomes. The first patient was a 64-year-old Caribbean woman who had been living in Rome for more than 30 years. She was referred to our clinic in December 2005 because of anemia. Her past medical history was unremarkable. In particular, she did not use alcohol, drugs or tobacco. Her nutritional status was very good. The physical examination was unremarkable, with the exception of pallor; the Received: April 30, 2007 Accepted after revision: July 12, 2007 Published online: September 21, 2007

Managing myelodysplastic syndromes in very old patients: a teaching case report.

The introduction of hypomethylating agents in the treatment of myelodysplastic syndromes (MDS) has significantly changed the clinical scenario of these diseases, which afflict predominantly older individuals. However, some concerns regarding the optimal application of these innovative and costly agents in the treatment of geriatric high-risk MDS remain. We report here the case of a nonagenarian treated with hypomethylating agents achieving a long-lasting clinical response and a significant improvement in her functional status. Our case confirmed that functional status and biological status, rather than the chronological age alone, can substantially guide the plan of an appropriate treatment strategy in high-risk MDS patients; moreover, the current case emphasizes the need for targeted studies in the field of geriatric MDS in order to formulate guidelines on the appropriate use of these costly agents, so that candidate patients can receive adequate treatment to preserve their quality of life and life expectancy, but at the same time avoiding unnecessary costs deriving from the use of high-cost drugs for those in whom a significant therapeutic result cannot be reasonably expected.

Primary diffuse large B-cell lymphoma of the bone marrow in a frail and elderly patient successfully treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

TO THE EDITOR: The involvement of bone marrow (BM) in aggressive non-Hodgkin lymphomas (NHLs) usually indicates systemic dissemination. However, although uncommon, extranodal involvement of the BM as an isolated and unique localization of aggressive NHLs [1] such as anaplastic large cell lymphoma [2] or diffuse large B-cell lymphoma (DLBCL) [3-6], has also been reported. In particular, primary DLBCL of the BM is a rare type of extranodal lymphoma with poor prognosis [1, 4]. Approximately 10 cases of primary DLBCL of the BM have been described thus far [3], and few of them have been reported in individuals of very advanced age. Here, we report a case of primary DLBCL of the BM that was successfully treated using rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP chemotherapy; 3-week standard schedule) in a frail 76-year-old woman.