Light chain amyloidosis: Experience in a tertiary hospital: 2005-2013. / Amiloidosis de cadenas ligeras: experiencia en un hospital terciario 2005-2013.

BACKGROUND AND OBJECTIVES: AL amyloidosis is a rare condition whose management is undergoing changes due to recent advances in diagnosis and treatment. We describe a contemporary series of patients with AL amyloidosis to analyze the features that enable early diagnosis and optimal management. PATIENTS AND METHODS: We recruited for analysis 32 patients (19 women; mean age, 63 years) treated consecutively at our center. RESULTS: Eighty-four percent of the patients presented with asthenia, dyspnea or edema, with a previous duration of symptoms of 8 months (median). Cardiac (21/32) and renal impairment were the most common type (11/32). All of the patients, except one, had a monoclonal component in serum/urine or abnormal values for free light chains (78%, λ). The bone marrow (BM) showed clonal plasmacytosis in 29 cases. All of the cardiac biopsies and 50% of the BM biopsies showed amyloid deposits. The results of the echocardiogram and/or cardiac resonance were abnormal in 27/30 cases. The median NT-proBNP value at diagnosis was 5200 ng/ml. Thirteen patients died due to heart failure, 2 due to rejection after heart transplantation, 2 due to pneumonia and 1 after a stroke. Ten patients did not undergo treatment, 12 were treated with bortezomib and 5 were treated with alkylating agents. Five patients underwent heart transplantation and 4 underwent autologous bone marrow transplantation. Fourteen patients achieved a complete hematologic response and 10 achieved organ response. The median survival was 17 months. CONCLUSIONS: Cardiac involvement is the major determinant of prognosis. Yield of involved organ biopsy is high (100% heart biopsies). Antineoplastic treatment with bortezomib and/or autologous bone marrow transplantation achieves hematological responses with improvements in organ impairment.

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor.

Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are well-documented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure-'dual CB/TPD-MHSC transplant'-that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor.

This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16-60 years) and weight 70 kg (43-95 kg), received CBTs (median 2.39 x 10(7) total nucleated cell (TNC) per kg and 0.11 x 10(6) CD34+ per kg) and TPD-MHSC (median 2.4 x 10(6) CD34+ per kg and 3.2 x 10(3) CD3+ per kg). Median time to ANC and to CB-ANC >0.5 x 10(9)/l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets >20 x 10(9)/l was 32 days (MCI 0.78). MCI for grades I-IV and III-IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI=0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan-Meier) were 56 % and 47% (63% and 54% for patients

Hemophagocytic syndrome associated with retinoic acid syndrome in acute promyelocytic leukemia.

A 56-year-old woman with an acute promyelocytic leukemia (APL) developed a severe all-trans-retinoic (ATRA) syndrome on day 17 of treatment. Shortly after, she presented a picture of pancytopenia, hepatosplenomegaly, increased triglycerides, ferritin, and liver enzymes. A bone marrow biopsy showed abundant macrophages and no evidence of leukemia. Tests for secondary hemophagocytic syndrome (HPS) were negative. A diagnosis of HPS was made. Treatment with dexamethasone and high-dose immunoglobulins was unsuccessful. Consolidation chemotherapy with idarubicin and ATRA rapidly reversed the HPS. The HPS in this patient could be related to the release of macrophage-stimulating cytokines by APL cells during ATRA syndrome.

Translocation t(4; 6)(q21; q27) in a case of primary thrombocythaemia in transformation.

We report a case of primary thrombocythaemia showing a translocation t(4; 6)(q21; q27) five years after diagnosis. The patient had been treated with hydroxyurea. The clinical picture at the time was consistent with transformation. Karyotypic abnormalities are rare in this disease and are reviewed.

Peripheral thrombocytopenia, accessory spleen and Hodgkin's disease: an unusual combination.

A 32-year-old male developed severe autoimmune thrombocytopenia refractory to conventional immunosuppression. He had been treated with radiotherapy for stage I-A Hodgkin's disease (HD) 2 years earlier after a staging laparotomy and splenectomy. A 3-cm accessory spleen was detected using computed tomography scan and 99mTc scintigraphy. Resection resulted in normalization of the platelet counts. Two years later the patient remains in remission of both diseases. Immune thrombocytopenia is rarely associated with HD and its remission following resection of an accessory spleen is an unusual finding.

Deletion(2)(p23) abnormality in a case of secondary acute myeloid leukemia.

We report a case of acute myeloid leukemia (M5a of the FAB classification), secondary to the myelodysplastic syndrome, showing a deletion of the short arm of chromosome 2 at p23 in the bone marrow cells. In addition, a duplication of chromosome 13,dup(13)(q12q14) was found.

Unusual translocations and other changes in acute leukemia.

We report three cases of ANLL and one case of ALL in which we found chromosome abnormalities not previously described. The first patient had a (9;11;16)(p22;q23;p13) translocation in the relapse after bone marrow transplantation. In the second case, a secondary leukemia following a Wilms' tumor, there was a single chromosome anomaly, an inversion of chromosome 13. The third case also presented an isochromosome 13q. In the fourth patient we observed a translocation between two achrocentric chromosomes, as in the third patient, but not of the Robertsonian type: t(21;21)(q22.1;q22.5).

Bleeding in acute promyelocytic leukemia (APL): fibrinolysis or defibrination?

The coagulation abnormalities in 20 cases of acute promyelocytic leukemia (APL) treated at a single institution were reviewed. A remarkably uniform picture of defibrination and increased FDPs with well-preserved levels of other coagulation factors including AT-III was seen. Our data, together with those available in the literature, do not support DIC as the underlying mechanism of bleeding but seem rather to point to increased proteolysis as the cause.

[Remission induction treatment in adults with acute myeloid leukemia. 8-year experience with 2 successive protocols]. / Tratamiento de inducción la remisión en adultos con leucemia aguda mieloide. Ocho años de experiencia con dos protocolos sucesivos.

We report our eight year experience remission induction therapy in adult patients with acute myeloblastic leukemia. Overall 67 patients were treated, with a mean age of 43.3 years (range 15-75). Two treatment protocols were used. Complete remission (CR) was achieved in 23 patients of 39 receiving protocol A (58%). The 28 last patients were treated with the more aggressive protocol B, and CR was achieved in 23 patients (82%). CR was achieved in 68% of the overall group. The most outstanding predictive factors were age above 30 years, and M-5 morphology as indicating a poor prognosis.