[Donor leukocyte infusion after allogeneic stem cell transplantation]. / Infusão de leucócitos de dador após a transplantação alogénica de células estaminais.

Adoptive cellular immunotherapy with donor leukocytes of patients submitted to allogenic stem cell transplantation has had significant success in the past few years, especially in the treatment of primary disease relapse and in the prevention and treatment of some post-transplant infectious complications. Most patients treated with donor leukocytes had a relapse of chronic myelogenous leukemia, which was successfully re-induced into remission. The most significant toxicities of this treatment are the development of graft versus host disease and marrow aplasia. Three strategies were developed to limit the former: the infusion of graded doses of donor leukocytes, the depletion of CD8+ cells and the transfer of donor leukocytes transvected with a timidine kinase gene, which renders these cells sensitive to gancyclovir. The post-transplant infectious complications treated successfully with donor leukocytes were Epstein-Barr virus-induced lymphoproliferative disorders and cytomegalovirus infection. The former, arising most frequently in recipients of unrelated and/or mismatched T-cell depleted grafts, were treated with donor unseparated leukocytes or Epstein-Barr virus-specific T-cells. Cytomegalovirus infection in the early post-transplant period was largely prevented by the infusion of virus-specific T-cell clones, which restored donor-specific immunity to cytomegalovirus in the recipient.

[Treatment of acute promyelocytic leukemia with trans-retinoic acid. Experience of the Santa Maria Hospital, Medical School of Lisbon]. / Terapêutica da Leucemia promielocítica aguda com ácido Trans-Retinóico. Experiência do Hospital de Santa Maria, Faculdade de Medicina de Lisboa.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia that is usually associated with a fatal hemorrhagic diathesis. All trans-retinoic acid (ATRA) is an active metabolite of vitamin A that differentiates the malignant cell clone, corrects the coagulopathy, and induces complete remission in the vast majority of patients with APL. Between June 1992 and September 1993, 8 patients with APL (4 previously untreated, 3 in first relapse and 1 in second relapse) received ATRA. Complete remission was achieved in 7 patients; in 5 with ATRA alone and in 2 with ATRA followed by cytotoxic chemotherapy due to the development of asymptomatic hyperleukocytosis. The earliest signs of response were the correction of the coagulopathy and an increase in the white blood cell count. Sequential morphological and immunophenotypical analyses of the bone marrow revealed differentiation of the malignant cell clone, in the absence of bone marrow hypoplasia. 4 of 5 patients treated only with ATRA until complete remission had late leukopenia. The most frequent adverse effects were dryness of skin and mucosae, hypertrigliceridemia and hypercholesterolemia, and a moderate increase in liver transaminases. An increase in the white blood cell count was common, and in two cases exceeded 35.0 x 10(9)/l. One of these patients developed multiple thrombosis of the extremities after cytotoxic chemotherapy. We frequently observed an increase in lactic dehydrogenase levels that was concomitant with the peak in the white blood cell count. The only patient on whom complete remission was not achieved was 60 years old, had chronic obstructive pulmonary disease, and died in the third week of therapy with a pulmonary distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute promyelocytic leukemia. The therapeutic advances]. / Leucemia promielocítica aguda. Avanços terapêuticos.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia. It is frequently associated with a life-threatening hemorrhagic diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with APL have bone marrow infiltration by abnormal promyelocytes, usually with prominent cytoplasmic granulation. These patients have a unique cytogenetic abnormality, a balanced reciprocal translocation between the long arms of chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on chromosome 17, is translocated to the PML gene region, on chromosome 15, resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR-alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase chain reaction. This assay is extremely useful in the diagnosis and detection of minimal residual disease in APL patients. All trans-retinoic acid (ATR) differentiates the malignant cell clone and corrects the coagulopathy associated with this disease. The most important adverse effect is a respiratory distress syndrome, treatable with steroids, if detected at its onset. ATR yields durable remissions in patients with APL, after consolidation with cytotoxic chemotherapy.