Carmen Jiménez

Morbidity and transplant-related mortality of CBV and BEAM preparative regimens for patients with lymphoid malignancies undergoing autologous stem-cell transplantation

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkins lymphoma (69) and Hodgkins disease (44) undergoing ASCT between 1990 – 2004. CBV (cyclophosphamide, 6000 mg m−2; VP-16, 750 mg m−2; and high-dose BCNU, 800 mg m−2) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m−2; VP-16, 800 mg m−2; cytarabine, 800 mg m−2; melphalan, 140 mg m−2). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.

Development of non-ABO RBC alloantibodies in patients undergoing allogeneic HPC transplantation. Is ABO incompatibility a predisposing factor?

BACKGROUND: Data from the appearance of RBC antibodies other than ABO in patients undergoing HPC transplantation are limited.

Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

BACKGROUND: A patient who received an ABO‐incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41‐year‐ old man with chronic myeloid leukemia received an ABO‐incompatible bone marrow graft from his HLA‐identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous‐flow blood cell separator. The patient was given group O Rh‐positive RBCs and group A Rh‐positive platelets. Prophylaxis for graft‐versus‐host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti‐K, anti‐Jk(b), anti‐M, IgG anti‐A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b‐), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti‐M, anti‐Jk(b), and anti‐K. During the second hemolytic episode (Day 35), the patients blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti‐M, anti‐Jk(b), and IgG anti‐A were detected in the serum. Eluates made from the recipients RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d‐), and anti‐Jk(b) and IgG anti‐A were observed in the serum and in an eluate made from the patients RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.

FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Forty-five patients with high-risk myeloid malignancies (32 acute myeloid leukemia and 13 high-risk myelodysplastic syndromes) were treated with fludarabine, cytarabine, idarubicin, and G-CSF (FLAG-IDA). Twenty-four (53%) patients achieved complete remission (CR), and five (11%) partial remission. Infection predominantly with pulmonary involvement was the most common regimen-related toxicity. Mucositis (15 patients) and pulmonary toxicity (19 patients) were the most frequently observed non-hematologic side effects. There were four early deaths and 12 patients presented with resistant disease. Overall survival (OS) at 12 months was 40%. The FLAG-IDA regimen shows evident antileukemic activity in patients with high-risk myeloid malignancies with acceptable toxicity.

Graft-versus-tumour effect in non-small-cell lung cancer after allogeneic peripheral blood stem cell transplantation

Clinical evidence of a graft‐vs.‐tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non‐small‐cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft‐vs.‐host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.

Recent improvements in outcome for elderly patients with de novo acute myeloblastic leukemia.

A retrospective analysis was performed on 263 consecutive patients aged over 60 with de novo acute myeloid leukemia (AML) diagnosed in a single institution between 1979 and 1998. Eighty-nine patients (33%) received only palliative treatment, while 174 patients (67%) were treated with different intensive chemotherapy regimens. The 5- and 10-year overall survival (OS) for the whole series was 7.7+/-1.2 and 4.3+/-1.6%, respectively. For patients receiving chemotherapy, OS was 10.5+/-2.5 and 7+/-2.6%, while for those patients receiving supportive treatment it was 1.1+/-1.1 and 0%, respectively (P=0.002). Within the group of patients receiving chemotherapy, the complete remission (CR) rate was 46%; treatment failure rate was 54% (36% due to treatment-related mortality and 18% due to resistant disease). Variables influencing CR rate were FAB subtype, CD7 positivity, chemotherapy regimen, creatinine level, hepatomegaly, and period of diagnosis. Median disease-free survival (DFS) duration was 8.4 months with a probability of being disease-free at 10 years of 10+/-5%. There were no significant differences in DFS according to age. According to the period of diagnosis (1979-1986 vs. 1987-1998), improvements in the CR rate (27 vs. 56%, P=0.0002), and OS (10.9 vs. 15.7 months, P=0.0007) were observed. This large single-center study of unselected de novo AML elderly patients substantiates the progressive improvement achieved in the management of elderly patients with AML, probably due to an improvement in supportive care and the administration of conventional induction chemotherapy.

Essential monoclonal gammopathy with an IgM paraprotein that is a cryoglobulin with cold agglutinin and EDTA-dependent platelet antibody properties

A patient with apparent anaemia and thrombocytopenia caused by a monoclonal paraprotein is described. The patients serum contained a monoclonal IgM kappa, a cryoglobulin and a cold agglutinin. The cryoglobulin, similar to the serum paraprotein, was a monoclonal IgM kappa. Serum was studied to determine the relationship of the cryoglobulin with the cold agglutinin. The cryoglobulin and cold agglutinin were found to be the same paraprotein. Moreover, with absorption and elution techniques the reactivity of the autoantibody with both erythrocytes and platelets was demonstrated.