Gianna Maria D'Elia

Pleural-pericardic effusion as uncommon complication in CML patients treated with Imatinib

To the Editor: Imatinib is usually well tolerated and has significant anti-leukaemic activity in chronic myeloid leukaemia (CML) patients (1). The most frequent adverse events that appear to be related to this drug are nausea, oedema, myalgias and cutaneous rashes (2). We describe a pleural-pericardic effusion as uncommon complication that occurred in three patients during imatinib treatment. The first patient was a 61-yr-old CML female who, after an initial phase of treatment with interferon-a, experienced a lymphoid blast crisis (BC). She started imatinib in October 2001 and returned to a chronic phase (CP) with a complete haematological (CHR) and cytogenetic response (CCR) obtained after 2 months of treatment. At week 40, the patient developed weakness, progressive dyspnoea and weight gain, associated to bilateral pleural effusion and large pericardial effusion detected by echocardiography. Bone marrow analyses confirmed the patient being in CP and in CCR. The patient was treated with diuretics (furosemide at the dose of 40 mg/d) and steroids (prednisone at the dosage of 0.25 mg/kg), while imatinib was discontinued for 3 wk. Two weeks later, symptoms had completely resolved and imatinib was restarted at 400 mg/d. The second patient was a 41-yr-old male with myeloid BC, which after 3 wk of imatinib treatment at the dose of 600 mg/d, developed chest pain with progressive dyspnoea and weight gain. Echocardiography revealed a pericardial effusion and chest X-ray showed a left-pleural effusion. Imatinib was discontinued and steroid therapy (prednisone, 0.25 mg/kg) was started. Bone marrow analysis showed the patients being in persistent CP. After 3 wk the effusions resolved and imatinib was restarted at initial low dosage of 300 mg/d and then restarted at 600 mg/d. The third patient was a 72-yr-old female with a myeloid BC that developed dyspnoea and weakness after 54 wk of imatinib treatment at 600 mg/d, with which had obtained CHR. A chest X-ray showed a bilateral pleural effusion and an echocardiogram revealed a collapse of the right atrium and ventricle, caused by a large pericardial effusion. Imatinib was discontinued and steroid therapy (prednisone at the dosage of 0.25 mg/kg) and diuretics (furosemide, 60 mg/d) were started and continued for 3 wk. Also in this case bone marrow morphology showed the persistence of CP. Imatinib was restarted at 400 mg/d after the effusions had resolved. In all patients, cytospins of pleural fluid samples were analysed, but no evidence of extramedullary leukaemic infiltration was detected. Under imatinib therapy, fluid retention events may occur more frequently in BC patients (up to 16%, as stated by Prod Info Gleevec, 2001, Novartis Pharmaceuticals Inc., Dorval QC, Canada), but are less common in CP patients and are reported among the grade 3–4, only in patients treated with high dosage (600 mg and over) (2, 3). Pleural and pericardial effusions are considered among the grade 3 and 4 of oedema. In literature only one specific case of CML patient was reported, that developed cardiac tamponade under imatinib treatment at the dose of 400 mg/ d (4). In the present cases, we have excluded that the effusions were caused by progression of disease, but probably occurred, in the absence of heart failure and infectious causes, as a result of imatinib treatment at higher doses. The fact that with the discontinuation of imatinib, the weight gain and the effusions rapidly resolved, also suggest that this uncommon events are caused by imatinib. In fact, it is well described that this drug may have an effect on fluid dynamics and may cause a potential retention in visceral spaces. In conclusion, we suggest a close monitoring of patients treated with imatinib at dose of 600 mg/d and over and the preventive use of diuretics during the treatment. Eur J Haematol 2005: 74: 89–90 All rights reserved Copyright Blackwell Munksgaard 2005

Granulocytic sarcoma of the pancreas successfully treated with intensive chemotherapy and stem cell transplantation

Abstract: A case of preleukemic granulocytic sarcoma of pancreas is presented. Pancreas is a well described site of secondary metastasis of solid tumors, but occasionally it has been reported as the primary site of leukemia. Like other cases reported in the literature, the present case was initially misdiagnosed as malignant lymphoma. We highlight the importance of an accurate immunohistochemical diagnosis and of an early and intensive acute myeloid leukemia‐like treatment for these cases representing an uncommon and aggressive form of acute leukemia.

Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI-1-positive, 3q21q26 syndrome and T cell-line antigen expression: what is the EVI-1 gene role?

Summary. Two cases of acute myeloid leukaemia (AML) with CD2 and CD7 expression associated with diabetes insipidus (DI) as the initial symptom are presented. Both patients had t(3;3)(q21;q26) associated with monosomy 7 and EVI‐1 overexpression. No neurohypophysis infiltration was evident. One patient died during induction chemotherapy, the other did not respond to therapy and died with persistent DI. Our findings further support the existence of a distinct AML entity characterized by the presence of DI, abnormalities of chromosome 3q, dysmegakaryopoiesis and poor outcome, and provide evidence of EVI‐1 gene involvement. The possible role of chromosome 3q26 abnormalities in determining this peculiar clinical–biological association is emphasized.

Granulocytic Sarcoma with Breast and Skin Presentation: A Report of a Case Successfully Treated by Local Radiation and Systemic Chemotherapy

Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders, but can also occur without overt hematologic disease, i.e. in patients with a normal bone marrow and no history of acute myelogenous leukemia. This primary extramedullary lesion may indeed represent a diagnostic and therapeutic dilemma for both the hematopathologist and oncologist. We describe a case of GS diagnosed in a nonleukemic patient and review the literature regarding the pathologic features and treatment of this condition.

Budd-Chiari syndrome as the first manifestation of polycythemia vera in young women with inherited thrombophilic state: an aggressive form of myeloproliferative disorder requiring multidisciplinary management.

Abstract:  The Budd‐Chiari syndrome (BCS), characterized by the obstruction and occlusion of the suprahepatic veins, is a rare but typical complication occurring in patients with polycythemia vera (PV). We describe three young women who developed BCS as first manifestation of PV, in association with an inherited thrombophilic state and in the absence of concomitant use of oral contraceptives. Our report illustrates the existence of an aggressive form of myeloproliferative disorder, which requires prompt recognition and immediate therapeutic intervention including cytostatic drugs and anticoagulant treatment. Furthermore, we suggest the need of routine screening for thrombophilic state in young women affected by PV.

Cutaneous pleomorphic T‐cell lymphoma coexisting with myelodysplastic syndrome transforming into acute myeloid leukemia: successful treatment with a fludarabine‐containing regimen

Abstract: The coexistence of a primary myelodysplastic syndrome (MDS) and a T‐cell cutaneous non‐Hodgkins lymphoma is an extremely rare event, which has so far only been reported in a single instance in the literature. We describe herein an additional case in which the lymphoid disease was combined with an MDS at the time of its evolution into acute myeloid leukemia (AML). Both diseases were successfully treated with a regimen containing fludarabine. We discuss possible pathogenetic mechanisms and suggest the use of nonalkylating drugs, such as fludarabine, for the treatment of this rare association of malignancies usually characterized by a very poor response to therapy.

Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: further evidence for the arbitrary nature of current classification systems.

From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2–8) developed a peripheral monocytosis >1 × 109/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.

Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait policy, and other therapeutic approaches in the rituximab era

Splenic marginal zone lymphoma (SMZL) is an indolent lymphoma in which watch and wait (W&W) approach as well as splenectomy and chemo-immunotherapy are usually recommended. The role of the different approaches in relation to risk factors was evaluated. One hundred patients with SMZL were retrospectively studied. Median age was 65 years. HCV positivity was 3.1%. The 10-year overall-survival was 95.1% (CI: 90-100%). Sixty-two asymptomatic, low tumour burden patients were submitted to W&W. A low-risk group not requiring treatment was identified. Patients requiring treatment received splenectomy (36), chemotherapy-alone (27) and rituximab ± chemotherapy (16). In multivariate analysis, negative predictors for starting treatment were female-sex, splenomegaly, ECOG ≥ 1. Patients with low IIL-Score had a better 5-year TFT (24%). The median TFT of the W&W cohort was 58.5 months; at 10 years, 17% of patients were still on W&W. Splenectomy and rituximab ± chemotherapy showed similar results, while chemotherapy alone proved inferior. This real-life single-centre study of SMZL confirmed its very good prognosis with a survival likelihood overlapping that of general population. The prognostic role of IIL-Score was confirmed. The W&W approach allowed a median PFS longer than in follicular lymphoma. Finally, our data confirm the inferiority of chemotherapy compared to splenectomy and rituximab±chemotherapy.

Paroxysmal cold haemoglobinuria as a tardive complication of idiopathic myelofibrosis

Abstract:  Paroxysmal cold haemoglobinuria (PCH) is an autoimmune haemolytic anaemia caused by the Donath–Landsteiner antibody. It is classically described in association with chronic syphilis or after acute viral infections. We describe the first case of PCH presented as a late manifestation of advanced myelofibrosis associated with antiphospholipid syndrome, that promptly responded to high dosage of prednisone.

Radiotherapy in indolent primary cutaneous B-cell lymphoma

Radiation therapy (RT) remains a powerful single option with curative intention in the local treatment of indolent primary cutaneous B‐cell lymphoma (pcBCL). It is well known that (1) primary cutaneous marginal zone lymphoma (pcMZL) have a much higher relapse rate than primary cutaneous follicle center lymphoma (pcFCL) after RT, (2) pcFCL and pcMZL present at different skin sites, and (3) pcMZL much more often present with multifocal lesions than pcFCL. We presented an analysis of retrospective cohort investigating the role of initial RT in patients with an indolent pcBCL. A radiation dose of 20 to 46 Gy was prescribed. With 131 months (range, 25‐240) follow‐up, we concluded that lesions at other sites than the trunk and the presence of multiple lesions were associated with an increased relapse risk on the basis of a difference in 5‐year relapse‐free survival (RFS) rate for patients with trunk lesion versus those with other location (89.4% versus 66.9%) and in case of single and multiple lesions (83.5% versus 57.1%, P = .04). Several important issues still need to be discussed. First, the multiple lesions definition could be a confounder. We classified multifocal lesions as those lesions requiring different radiation fields. Second, the substantial variation in radiation dose used (20 to 46 Gy) could potentially increase selection bias in this kind of analysis. Indolent pcBCL is a high radioresponsive disease and dose over 30 Gy is unusual, especially in radiosensitive organs such as the eye. With regard to pcBCL, the high total dose up to 46 Gy was prescribed in order to control the disease on a long‐term basis. We have reported excellent clinical outcomes with 10‐year RFS and overall survival rates of 71.1% and 87.1%, respectively. No in‐field recurrences were observed. This high total dose could potentially improve severe late toxicity, including the risk of RT‐induced second malignancies, although dose distribution was just limited to skin zone. We recognize that it could represent an overtreatment, based on current guidelines, but the tumor size at diagnosis could justify 30 to 46 Gy as an appropriate dose, when the intent for treatment was tumor eradication. Surely, this was only one retrospective experience, but we believe it could provide an appropriate tool for a better issues awareness. The use of low‐dose involved‐field RT for indolent pcBCL is generally scheduled in palliative setting. Low doses of 4 Gy have been shown