Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda / Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia

Background: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. Aim: To report our experience with HSCT in patients of different ages with acute leukemia. Material and Methods: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. Results: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. Conclusions: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

Tratamiento de anemia aplásica severa adquirida en pacientes pediátricos con inmunosupresión y trasplante alogénico de precursores hematopoiéticos / Treatment of acquired severe aplastic anemia in pediatric patients with immunosupression and allogeneic stem cell hematopoyetic transplant

Background: Severe acquired aplastic anemia (SAA) is an uncommon disease of childhood. Patients with SAA receive supportive care with transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be allogenic stem cell transplantation (SCT) from a matched sibling or immunosupressive therapy (IT). Aim: To report the experience in the management of SAA. Patients and methods: Twenty five children with acquired SAA were treated from July 1992 to September 2005. Patients with full matched sibling donors received allogenic SCT after conditioning with a cyclophosphamide containing regimen. The other patients received immune suppression with cyclosporine plus methylprednisolone (n= 18) plus ATG (n=17). All received supportive care until recovery of hematopoietic function. Those who had severe opportunistic infections at diagnosis or did not respond to two cycles of ATG were evaluated for unrelated donor SCT. Results: Seven patients received sibling donor SCT and 18 IT, which was repeated in six. Three patients received mismatched related (1) or unrelated (2) SCT. Nineteen patients survived with a median follow up time of 4 years, 14 with full hematologic recovery. Six patients died: four due to infections after IT or SCT, one due to intracranial hemorrhage and one with secondary myelodysplasia 12 years after IT. Conclusions: Most children with SAA can be treated successfully with sibling donor SCT or IT. Patients without a histocompatible sibling who fail to respond to IS have a worse prognosis.

Tratamiento endovascular del síndrome de vena cava superior / Endovascular treatment of superior vena cava syndrome

Background: Superior vena cava syndrome (SVCS) is caused by the obstruction of venous drainage from the upper portion of the body. Common clinical findings are headache and cervical, facial and upper limb edema. Occasionally, clouding of consciousness appears. Aim: to report our experience with endovascular treatment of SVCS. Material and methods: Retrospective review of all patients with SVCS subjected to endovascular treatment between 1999 and 2005. Results: Eight patients were treated, all of them with malignancies. Six had a benign obstruction due to the presence of a chemotherapy catheter located in the superior vena cava, one had obstruction secondary to radiation therapy and one a tumor compression of the superior vena cava. Two patients underwent thrombolytic therapy. Angioplasty and stenting was performed in all patients. The chemotherapy catheter was removed to all patients and installed again in one. One patient had a hemothorax secondary to a simultaneous needle lung biopsy under video thoracoscopy. No patient died in relation to the procedure. Congestive signs and symptoms subsided in all patients within 24 hours after the procedure. During follow up, only one patient had symptoms related to vena cava obstruction and three died due to their malignant tumor. Conclusions: Endovascular treatment of SVCS has a low rate of complications and provides immediate and mid-term symptom relief.

Síndrome de lisis de glóbulos blancos después de un trasplante autólogo de células troncales hematopoyéticas en el tratamiento de la amiloidosis AL renal: Caso clínico / White blood cell lysis syndrome after autologous peripheral blood stem cell transplantation in the treatment of renal AL amyloidosis: Case report

The treatment of AL amyloidosis was not successful until the advent of myeloablative chemotherapy consisting of high-dose intravenous melphalan followed by autologous peripheral blood stem cell transplantation. This new treatment has achieved better survival rates and, remarkably, it has obtained complete remission. Among patients with renal involvement, achievement of a complete hematological response was associated with a 50% reduction in proteinuria and stable creatinine clearance in more than 2/3 of patients. Despite of these excellent results, this new therapy is associated with significant toxicity, including the development of acute renal failure due to white blood cell lysis syndrome. We report a 59 year-old female with a nephrotic syndrome due to primary amyloidosis successfully treated autologous stem cell transplantation who developed acute renal failure caused by white blood cell lysis syndrome. The patient required treatment with granulocytic colony stimulating factor and intermittent hemofiltration and was discharged 23 days after melphalan administration with a satisfactory renal function and white blood cell count. After one year of follow up, she maintains a good glomerular filtration rate, a proteinuria of less than, 1 g/day and normal hematological values.

Leucemia de células natural killer: Caso clínico / Natural killer cell leukemia: Case report

Natural killer leukemia is a rare and highly aggressive neoplasm, is more common in young male patients and has a very poor prognosis, with a median survival of few weeks. We report a 17 years old male patient who developed, after an acute upper respiratory disease, a rapidly multiorganic failure with pancytopenia. Bone marrow aspiration and trephine biopsy showed an acute lymphoblastic leukemia. The immunophenotype and immunohistochemistry revealed a natural killer acute leukemia. The disease progressed rapidly and the patient died shortly after the diagnosis.

Estudio piloto de la fusión PML/RAR alfa por el método de hibridación in situ con fluorescencia, FISH, en leucemia aguda promielocítica / Pilot study of PML/RARalfa fusion by fluorescence in situ hybridization, FISH, method in acute promyelocytic leukemia

Background: Acute promyelocytic leukemia (APL) is characterized cytogenetically by t(15;17) (q22;q21) and its molecular consequence, fusion of PML and RAR_ genes. The detection of this genetic marker confirms the diagnosis and allows monitoring of the leukemic clone during treatment, which has prognostic value. Cytogenetics fails in some cases due to the absence of metaphases in cultures or their bad morphology. Southern blot and PCR methods require trained personnel and adequate equipment. FISH method allows the identification of chromosomic rearrangements in 24 to 48 h and is simple to set up in a cytogenetics laboratory. Aim: To evaluate the FISH method to detect PML/RAR_ fusion, compared to cytogenetic analysis. Patients and methods: Fifteen bone marrow specimens from APL patients with previous cytogenetic analysis were studied, using a commercial probe to detect PML/RAR_ fusion. Results: We obtained a normal cut-off value of 9.1 percent. Specificity and sensibility were 100 percent. Six positive cytogenetic cases at diagnosis were FISH positive. Six negative cytogenetic cases, one APL at diagnosis and five normal controls were FISH negative. One case in remission, that was negative by cytogenetics, was positive near the cut-off value by FISH. Two other cases in remission, not conclusive by cytogenetics, were negative by FISH. Conclusions: FISH is a reliable, rapid and relatively low cost method that can be used as an adjunct to conventional cytogenetics

Neoplasia endocrina múltiple tipo 2A: presentación de un caso de evolución inhabitualmente agresiva / Multiple endocrine neoplasia type 2A: report of a case with an aggressive outcome

We report a 28 years old woman who consulted for diarrhea of 2 years and thyroid nodule. A medullary thyroid carcinoma was diagnosed and a thyroidectomy performed. There was a local relapse 2 months later and distant metastases were found 5 months later. A MIBG-1131 scontigraphic image of the adrenal lead to the suspicion of a bilateral pheochromocytoma. The surgical resection of the adrenals confirmed the diagnosis. There was no response to chemotherapy and the patient continued with severe hypercalcemia, repeated infections, persistent diarrhea and cachexia, dying one year after the aggressive presentation of a multiple endocrine neoplasia type 2A

Trasplante de médula ósea en el tratamiento de enfermedades hematológicas malignas / Allogenic bone marrow transplantation in patients with malignant hematological diseases

We have treated 28 patients (pts) with malignant hematological diseases with allogenic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11.24 pts had a full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft vesus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57 percent at 36 months. Allogeneic BMT is an effective and feasing therapeutic procedure for selected patients with hematological malignancies