Alterations in bone mineral density and bone turnover markers in newly diagnosed adults with lymphoma receiving chemotherapy: a 1-year prospective pilot study.

BACKGROUND: Bone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy. PATIENTS AND METHODS: This was a prospective, single-center study conducted in patients aged≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated. RESULTS: Forty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19-86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III-IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7%±3.9% for lumbar spine (P<0.001), -2.2%±7.6% for femoral neck (P<0.01) and -2.6%±4.5% for total hip (P<0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P=0.01), higher lactate dehydrogenase level (P=0.04) and lower creatinine clearance (P=0.01); (ii) at total hip: lower albumin (P=0.01), higher corrected serum calcium (P<0.01), lower alkaline phosphatase (AP) (P<0.01) and autologous stem cell transplant (P=0.03); and (iii) at femoral neck: higher corrected serum calcium (P=0.02) and lower bone AP (P=0.01). CONCLUSION: Adult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.

Drug rash with eosinophilia and systemic symptoms after chlorambucil treatment in chronic lymphocytic leukaemia.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction with a long duration of eruption and serious organ involvement. The mortality rate has been estimated at about 10%. Aromatic anticonvulsants, sulphamides, minocycline and more rarely carbamazepine are the principal responsible drugs. We report the first case of chlorambucil-induced DRESS syndrome in a 70-year-old man recently diagnosed with chronic lymphocytic leukaemia. He developed recurrent skin rash, fever, hypereosinophilia, and acute renal failure after rechallenge with chlorambucil. The condition improved slowly after stopping medication and systemic steroids. Prompt recognition of a chlorambucil drug reaction is essential in patients receiving chemotherapy.

Myelofibrosis and cytopenia are not always malignant.

Myelofibrosis (MF) is characterized by reticulin fibrosis of the bone marrow. It may occur in neoplastic disorders such as myelofibrosis with myeloid metaplasia (MMM) or other neoplasms involving the bone marrow. However, autoimmune phenomena have been described in patients with MF defining a distinct clinicopathological entity called autoimmune myelofibrosis (AIMF). We report two cases of AIMF and review the literature.

Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

CD66c expression in B-cell acute lymphoblastic leukemia: strength and weakness.

INTRODUCTION: In B-cell acute lymphoblastic leukemia (B-ALL), testing at diagnosis for BCR/ABL1 gene rearrangements is mandatory for prognostic stratification and treatment decisions. Several diagnostic methods have been proposed using flow cytometry to identify BCR/ABL1(+) B-ALL. METHODS: We evaluated expression of the myeloid antigen CD66c by flow cytometry in B-ALL. We studied 94 patients with B-ALL. The t(9;22)(q34;q11) or BCR/ABL1 rearrangement was detected by cytogenetic analysis or RT/PCR. Myeloid antigens CD66c, CD13, CD33, CD117, Myeloperoxidase, CD15 and CD65 were determined by flow cytometry. RESULTS: Of these 94 cases, 17 (18%) cases displayed BCR/ABL1 gene rearrangements and 38 (40%) cases were CD66c positive. CD66c was the most common myeloid antigen expressed on malignant lymphoblasts. Its expression was correlated with BCR/ABL1 rearrangements (P = 0.0001): sensitivity 82%, specificity 69%, positive predictive value 37% and negative predictive value 95%. Co-expression of CD66c(+) CD13(+) was more frequent in BCR/ABL1(+) B-ALL (29%) than BCR/ABL1(-) cases (4%) (P = 0.0044). Some BCR/ABL1(-) B-ALL cases (including hyperdiploid or cases with normal karyotype) were CD66c positive (31%). CONCLUSION: CD66c expression is correlated, but not specifically, with BCR/ABL1 rearrangement. It would seem better to interpret the absence of CD66c expression with a lack of BCR/ABL1 rearrangement. This myeloid antigen could be interesting in the detection of minimal residual disease.

Myelofibrosis-associated lymphoproliferative disease: retrospective study of 16 cases and literature review.

Background. To better describe the clinical, biological, and the outcome of non-Hodgkin's lymphoma (NHL) with, at the initial presentation, bone marrow fibrosis (MF). Patients and Methods. From January 2001 to January 2007, 16 eligible patients with NHL and MF were retrieved from the Pathology Department of the University hospital of Amiens. Median age of patients was 62 years (range 16-74) with a sex ratio male/female of 3. Results. MF is associated with all types of lymphoma predominantly with B-cell phenotype and it seems to be more associated with low-grade NHL. B-symptoms are more frequent at diagnosis and more patients presented with an elevated LDH level. JAK-2 was negative in the 10 patients analysed. Two patients presented with features of primary MF with no evidence of lymphoma. Overall response rate was 94% after the first line of therapy with regression or improvement of MF. Relapse occurred in 8 patients (47%) with recurrence of MF in all of them. After a median follow-up of 42 months, 12 patients were alive with an overall survival rate for the entire group of 75%. Conclusions. MF-associated NHL is a rare manifestation which may be associated with all types of NHL and its presence does not seem to confer a poor prognosis. A search for lymphoproliferation should be considered when the cause of MF is not apparent.

First-line autologous stem cell transplantation in primary CNS lymphoma.

The treatment of primary central nervous system lymphoma (PCNSL) has been considerably improved over recent years. In this article, we report six cases of PCNSL treated by first-line induction chemotherapy followed by intensive chemotherapy and autologous stem cell transplantation (ASCT). Six immunocompetent patients presenting with a PCNSL, confirmed by thoraco-abdomino-pelvic computer tomography scan and bone marrow biopsy, were treated with induction chemotherapy followed by BEAM intensive chemotherapy and ASCT and radiotherapy. At the end of the treatment, all the patients were in complete remission. After a median follow-up of 41.5 months (17-70 months), four patients were alive without signs of relapse (median survival: 35.5 months). Two patients died from relapse at 19 and 23 months. The neurotoxicity was low with epilepsy in one patient and persistent left side dysesthesia in another one. These results are fairly encouraging. Other studies with greater numbers of patients and longer follow-up are needed to confirm this study.