Fuensanta Millá

Bone Marrow Changes in Anorexia Nervosa Are Correlated With the Amount of Weight Loss and Not With Other Clinical Findings

The clinical history and biochemical and hematologic variables for 44 consecutive patients diagnosed with anorexia nervosa were recorded. Bone marrow aspirates and biopsy specimens were analyzed by standard morphologic procedures, and bone marrow adipocytes were studied morphometrically. The bone marrow of the 44 patients was classified as normal (5 cases [11%]), hypoplastic or aplastic (17 [39%]), with partial or focal gelatinous degeneration (13 [30%]), or with complete gelatinous degeneration of the bone marrow (GDBM; 9 [20%]). These patterns correlated with amount of weight loss (P = .005) but not other clinical findings. WBC counts were lower in patients with GDBM (P = .0189), but this and other peripheral blood variables did not always reflect the severity of bone marrow damage. Hypoplastic or aplastic bone marrow showed an increase in bone marrow fat fraction due to an increase in adipocyte diameters, while in GDBM, fat fraction and adipocyte diameters decreased. Morphologic changes in bone marrow and stereologic alterations in bone marrow adipocytes may be observed in anorexia nervosa. The extent of damage is related to the amount of weight loss, not to other factors. Peripheral blood cell counts may not reflect the extent of damage. In some patients, this process may be reversible with reestablishment of adequate nutritional intake.

Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group.

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.

Influence of highly active anti‐retroviral therapy on response to treatment and survival in patients with acquired immunodeficiency syndrome‐related non‐Hodgkin's lymphoma treated with cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone

Combined highly active anti‐retroviral therapy (HAART) with protease and reverse transcriptase inhibitors has modified the natural history of opportunistic infections and neoplasms in human immunodeficiency virus (HIV)‐infected patients. We analysed the influence of HAART on the response to treatment and survival in a series of 58 patients with acquired immune deficiency syndrome (AIDS)‐related non‐Hodgkins lymphoma (NHL) treated with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone). Two groups of patients were included: (i) forty‐one patients diagnosed with NHL between 1988 and 1996 who were not treated with HAART; (ii) seventeen patients diagnosed since 1996, who were receiving or commenced HAART when NHL was diagnosed. The response rate to CHOP was higher in group 2 (13 out of 17 cases; 75%) than in group 1 (14 out of 41 cases; 34%) (P = 0·003). The 2‐year probability of event‐free survival (EFS) [95% confidence interval (CI)] for group 1 was 0·5 (0·24–0·74), whereas for group 2 it was 0·85 (0·61–0·90) (P = 0·024). The lymphoma‐free survival (LFS) was also significantly different for both groups (2‐year LFS probability 0·53 vs. 1·0, P = 0·04). The median (95% CI) overall survival (OS) for group 1 was 7 months (range, 3–10·8 months), whereas it was not reached in group 2 (P = 0·0015). In the multivariate analysis for remission attainment, the only variables with a higher probability to achieve complete remission (CR) were HAART (P = 0·01) and International Prognostic Index score 1 (P = 0·02). The only statistically significant variable in the multivariate analysis for EFS was HAART (P = 0·049) and the variables with prognostic value for OS in the multivariate analysis were B symptoms (P = 0·01) and HAART (P = 0·003). Patients with AIDS‐related NHL treated with CHOP and HAART had a higher CR rate than those treated only with CHOP. In this study, HAART was an independent prognostic factor for CR, OS and EFS in patients with AIDS‐related NHL.

Hepatosplenic T-Gammadelta Lymphoma in a Patient with Crohn's Disease Treated with Azathioprine

Hepatosplenic γ δ T-cell lymphoma (HS γ δ TCL) is an uncommon type of peripheral T-cell lymphoma, which has been associated in some cases with immunosuppression, mainly after solid organ transplants. We describe a case of HS γ δ TCL with a leukaemic course in a patient with Crohns disease who had received azathioprine during the previous 55 years. Sinusoidal infiltration by atypical lymphocytes was observed in the liver, spleen and bone marrow and the typical cytogenetic abnormalities (isochromosome 7 and trisomy 8) were found. The patient did not respond to intensive chemotherapy. This case shows the importance of ruling out HS γ δ TCL in patients with hepatosplenomegaly, B-symptoms and any immunosuppressive condition.

Incidence and Prognostic Impact of Secondary Cytogenetic Aberrations in a Series of 145 Patients with Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a mature B‐cell neoplasm with an aggressive behavior, characterized by the t(11;14)(q13;q32). Several secondary genetic abnormalities with a potential role in the oncogenic process have been described. Studies of large MCL series using conventional cytogenetics, and correlating with proliferation and survival, are scarce. We selected 145 MCL cases at diagnosis, displaying an aberrant karyotype, from centers belonging to the Spanish Cooperative Group for Hematological Cytogenetics. Histological subtype, proliferative index and survival data were ascertained. Combined cytogenetic and molecular analyses detected CCND1 translocations in all cases, mostly t(11;14)(q13;q32). Secondary aberrations were present in 58% of patients, the most frequent being deletions of 1p, 13q and 17p, 10p alterations and 3q gains. The most recurrent breakpoints were identified at 1p31‐32, 1p21‐22, 17p13, and 1p36. Aggressive blastoid/pleomorphic variants displayed a higher karyotypic complexity, a higher frequency of 1p and 17p deletions and 10p alterations, a higher proliferation index and poor survival. Gains of 3q and 13q and 17p13 losses were associated with reduced survival times. Interestingly, gains of 3q and 17p losses added prognostic significance to the morphology in a multivariate analysis. Our findings confirm previous observations indicating that proliferation index, morphology and several secondary genetic alterations (3q gains and 13q and 17p losses) have prognostic value in patients with MCL. Additionally, we observed that 3q gains and 17p losses detected by conventional cytogenetics are proliferation‐independent prognostic markers indicating poor outcome.

Predictive factors for poor peripheral blood stem cell mobilization and peak CD34+cell count to guide pre-emptive or immediate rescue mobilization

BACKGROUND AIMS Failure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilization. METHODS Data from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10(6) CD34(+)cells/kg body weight (BW). RESULTS The median age was 53 years (range 4-70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkins lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkins lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte-colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34(+)cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 10(6) CD34(+)cells/kg, with high sensitivity (90%) and specificity (91%). CONCLUSIONS The prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34(+) cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.

Incidence and characteristics of lymphoid malignancies in untreated myelodysplastic syndromes.

We have analyzed 1,198 patients with untreated myelodysplastic syndromes (MDS) with two main objectives: (1) to determine the prevalence of lymphoid malignancies (LM) in MDS patients; and (2) to ascertain whether there is some relationship between the MDS subtype and the LM type. In fourteen of 1,198 primary MDS patients (1%) (4 with refractory anemia, 3 with refractory anemia with ring sideroblasts, 2 with refractory anemia with excess of blasts and 5 with chronic myelomonocytic leukemia) a LM was detected. In all cases, the LM was of the B-cell type: 6 cases of chronic lymphocytic leukemia, 5 cases of lymphoplasmacytoid lymphoma, and 3 cases of multiple myeloma. B-cell malignancy did not prevail in any MDS subtype and no correlation was observed between the different varieties of both diseases. In conclusion, in this large series, 1% of the untreated patients with MDS had B-cell malignancy, an association that in most cases is likely to be merely coincidental.

Acute Promyelocytic Leukemia in a HIV Seropositive Patient

Acute myeloid leukemia (AML) is infrequent in patients with human immunodeficiency virus (HIV) infection. Among AML, acute promyelocytic leukemia (APL) has been rarely described in such patients, with only one case being published. We report a 30 years-old intravenous drug abuser HIV-infected male with APL who attained complete clinical, morphological, and molecular remission after differentiation therapy with all-trans-retinoic acid (ATRA) followed by intensive chemotherapy. The results of treatment in this patient and in other AML published cases suggest that therapy for AML should not be modified because of HIV infection if patients have an adequate performance status.

Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma.

Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.

Usefulness of tumor markers CA 125 and CA 15.3 at diagnosis and during follow-up in non-Hodgkin's lymphoma : study of 200 patients

CA 125 and CA 15.3 serum levels were measured at diagnosis, after treatment and at the time of recurrence in 200 consecutive patients (114 males, median age 56 years) with non-Hodgkins lymphoma (NHL) to explore its usefulness in the evaluation of response to treatment and survival in patients with NHL compared to lactate dehydrogense (LDH) and β2-microglobulin (β2-M). Their association with the clinical – biologic parameters at diagnosis, response to treatment, event-free survival (EFS) and overall survival (OS) was analysed. Eighty-six patients (43%) had elevated CA 125 levels and 35 (17.5%) had elevated CA 15.3 levels at diagnosis. CA 125 was associated with advanced stage, lung, pleural or gastrointestinal tract involvement and CA 15.3 was correlated with advanced stage, bone involvement, aggressive histology and bulky disease. LDH had the highest predictive value for failure to achieve complete remission (P = 0.001). A shorter OS was associated with increased LDH (P < 0.0001), β2-M (P = 0.013) and CA 125 (P = 0.025) whereas CA 15.3 was associated with a shorter EFS (P = 0.027). When elevated at diagnosis, CA 125 and CA 15.3 should be monitored during follow-up of patients with NHL.