Daniela Piccioni

Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy.

Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy

Pain syndromes in the setting of haematopoietic stem cell transplantation for haematological malignancies.

Severe pain syndromes may be recorded during all phases of haematopoietic stem cell transplantation (HSCT) for haematological malignancies: from stem cell mobilization to the long-term post transplant period. Although the major cause of pain in the setting of HSCT is injury to mucosal tissues induced by the conditioning regimen, pain from several other causes has been reported. In this paper, we review pain and its management in the setting of HSCT.

The Management of Membranous Glomerulopathy in Allogeneic Stem Cells Transplantation: Updated Literature

BACKGROUND membranous glomerulopathy (MG) is an immunomediated disorder which accounts for the most common cause of nephrotic syndrome (NS) following allogeneic hematopoietic stem cell transplantation (HSCT). OBJECTIVE AND METHODS to provide an update on the issue by reviewing pertinent literature on the MEDLINE database. RESULTS sixty-nine post allogenic HSCT patients (42 male) with MG were identified. The median age was 43 (5 to 68) years. Time interval from allogenic HSCT to MG diagnosis ranged from 3 to 134 months (median 17). Most MG patients had a history of acute (70%) or chronic (84%) graft versus host disease (GVHD). Corticosteroids and cyclosporine were the most common therapeutic agents used in this setting; alternative therapies, including rituximab, were given to a lower number of patients. Outcome data were available in 64 out of 69 MG patients; 38 (59%) and 18 (28%) patients achieved a complete and a partial response respectively, whereas treatment failure was recorded in the remaining 8 (13%). CONCLUSION MG after allogenic HSCT appears to be associated with a sub clinical or overt cGVHD, which follows the discontinuation of immunosuppressive prophylaxis. Although a standard therapeutic approach has not been established, the application of available measures can induce favorable response in more than 80% of affected patients, but treatment-failure and progressive deterioration of the renal function may occur in about one fifth of cases.

Contribution of immunophenotypic and genotypic analyses to the diagnosis of acute leukemia

Diagnostic accuracy in acute leukemia (AL) can be improved if traditional morphology and cytochemistry are supplemented with immunophenotypic and genotypic analyses. This multiparameter approach is of crucial importance for the management of patients, as it enables the identification of leukemic syndromes with distinct biological features and response to treatment. Immunophenotyping using monoclonal antibodies has been universally accepted as a useful adjunct to morphological criteria. This technique is particularly valuable in diagnosing and subclassifying acute lymphoblastic leukemia and is also essential in certain types of acute myeloid leukemia (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings can be quite helpful in establishing the correct diagnosis and can add information of prognostic significance. A number of specific chromosomal abnormalities have been recognized that are very closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis, the polymerase chain reaction, and fluorescence in situ hybridization. With the extensive use of these techniques it has become apparent that a proportion of leukemias exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand, apparently uniform chromosomal abnormalities such as the t(1;19) (q23;p13), t(9;22) (q33;q11), t(8;14) (q24;q32), or t(15;17) (q21;q21) may differ at the molecular level. Data collected from these modern technologies have introduced a greater complexity, which needs to be taken into consideration to improve both the diagnostic precision and the reproducibility of current classifications.

All-trans retinoic acid plus low doses of cytarabine for the treatment of "poor-risk" acute myeloid leukemias.

SummaryThirteen refractory/resistant AML patients no suitable for additional aggressive chemotherapy, were treated with a combination including all -trans retinoic acid (45 mg/m2 sine die) and low doses of Ara-C (20 mg/m2 subcutaneously, twice in a day, days 1–10, every 28 days). Ten patients were évaluable; 8 of them achieved a complete remission, two patients with an important tumor burden, failed to achieve a response. One complete remission patient relapsed after 7 months but is still receiving the same therapy and is now in partial remission. We believe this combination effective as inducer of complete remission in those AML patients which cannot tolerate additional heavy treatments. The role of tumor burden in affecting response to therapy remains to be still evaluated.

Mucositis in the treatment of haematological malignancies

Background. Mucositis is a highly significant and sometimes dose-limiting complication of many treatments given for blood-related neoplasia, representing a potential source of life-threatening infection and a major driver of total parenteral nutrition use, analgesic therapy, additional nursing care and longer hospitalisation. Aim and Methods. This review was based on a review of the most recent literature and on authors’ experiences, a summary of the current knowledge on mucositis has been provided together with the accepted recommendations on its management. Results. The incidence and severity of mucositis are influenced by patient and treatment variables, being particularly high in the setting of high dose chemotherapy and haematopoietic stem cell transplantation. A five-stage model has been identified in the pathophysiological process of mucositis. Although some interventions have been shown to be potentially effective, in many cases the reported clinical trials and the available data are inadequate to support the recommendation of the majority of agents. Thus, the only proven measures in the prevention of mucositis are cryotherapy and palifermin. Conclusions and perspectives. Further intensive research is necessary, through well-structured clinical trials, in order to obtain the best scientific evidence for agents to prevent and/or treat mucositis in the setting of haematological malignancies.

Feasibility of a dose-adjusted fludarabine–melphalan conditioning prior autologous stem cell transplantation in a dialysis-dependent patient with mantle cell lymphoma

Dear Editor, High-dose (HD) chemotherapy with autologous stem cell transplantation (SCT) has demonstrated to improve the outcome of relapsed aggressive non-Hodgkin lymphoma (NHL) and represents the current option of choice in suitable patients although it is associated with considerable acute and chronic toxicities [1]. In patients with renal failure, the treatment approach to aggressive NHL has not been stated. Moreover, conditioning regimens prior autologous SCT generally include HD of agents, which are contraindicated in the presence of severe renal impairment. Therefore, the application of myeloablative treatments to this category of frail patients remains a challenging concern. The case of a patient submitted to autologous SCT following conditioning with adjusted doses of fludarabine and melphalan (Flu/Mel) is here reported together with the description of the dialysis regimen adopted during the transplantation procedure. A 69-year-old male presented a second relapse of [AU1]mantle cell lymphoma after a 3-year maintained complete remission (CR). He received the rituximab, dexametazone, cisplatin and high doses of cytarabine (R-DHAP) regimen as salvage treatment. Unfortunately, during the first course of HD chemotherapy, he developed severe and unrecoverable renal impairment due to cisplatin toxicity for which he required dialysis on regular basis. The treatment resulted in a CR, as demonstrated by a body computed tomography scan and by bone marrow trephine biopsies. However, given the high risk of relapse, autologous SCT as consolidation was offered. The patient was properly informed and gave his consent. Therefore, 2 months after the completion of HD chemotherapy, stem cells were then regularly mobilized and collected after adjusted doses of intravenous (IV) cyclophosphamide (3 g/m 2 , day +1), followed by daily filgrastim (5 μ gk g �1 day �1 from day +5). After the stem cell collection, the patient was soon transplanted. Flu/Mel regimen was administered as conditioning at adjusted doses according to the dialysis-dependent renal failure and the patient’ sl ow performance status (Karnofsky score of 60%). Therefore, he received IV fludarabine at the dose of 6 mg m �2 day �1 × 4 days followed by IV melphalan 100 mg/m 2 the fifth day of

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,

Two antiemetic regimens do not impair chemical xenogenization induced in vivo by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide

SummaryThe possible interference with 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC)-mediated chemical xenogenization (CX) by antiemetic drugs was studied. DTIC was given alone or in combination with either dexamethasone or metoclopramide plus orphenadrine hydrochloride plus diazepam to CD2F1 mice bearing the histocompatible L1210 leukemia. Tumor cells were collected from treated animals and inoculated into histocompatible untreated and drug-treated recipients, for eight transplant generations. More than 50% of intact hosts rejected tumor cells between the fourth and sixth transplant generation, independently of antiemetic treatments. Positive controls treated with DTIC plus quinacrine (QC) confirmed that this antimutagenic compound entirely abrogates CX. The present results point out that the antiemetic regimens investigated in this study do not prevent CX. Since DTIC treatment requires intensive antiemetic support in man, these data are of clinical relevance for CX-oriented immunochemotherapy protocols.

The Prevention of Oral Mucositis in Patients with Blood Cancers: Current Concepts and Emerging Landscapes

BACKGROUND The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patients quality of life. OBJECTIVES To review currently available measures and investigational agents to prevent OM in hematological patients. METHODS we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. RESULTS/CONCLUSIONS Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.