Katia A.B. Eid

A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies

We present the results of a prospective, randomised study comparing PBPC and BM focusing on engraftment, acute and chronic GVHD and survival. Forty patients with haematological malignancies received HLA-identical sibling BM (group A) or PBPC (group B). Evaluable patients were 19 (A) and 18 (B). Median age was 35 (17–56) in A and 29.5 (9–51) in B. Conditioning was mainly Bu-Cy2; GVHD prophylaxis was CSA-MTX. PBPC were harvested after 5 days of G-CSF 10 μg/kg/day. Median days for an ANC >0.5  × 109/l was 18 (13–30) in A and 16 (11–25) in B (P = 0.10). Platelets >20 × 109/l occurred at +17 (10–40) in A and +12 (9–36) in B (P = 0.01). The probability of ⩾2 grade a-GVHD was 19% (A) and 27% (B) (P = 0.53). The probability of all grade c-GVHD was 70% with BM. In spite of the small number of patients in group B (PBPC), our data suggest the great majority of them will have c-GVHD (P = 0.08); extensive disease was present in 50 and 100%, respectively (P = 0.05). The estimates of overall survival for A and B at 1000 days are 51 and 47%, respectively (P = 0.67); DFS at 1000 days are 52 and 58%, respectively (P = 0.50). PBPC resulted in faster platelet engraftment. The incidence of acute and chronic GVHD was similar in both groups, but the severity of c-GVHD was higher with PBPC. No differences in survival and DFS have been observed to date.

Granulocytic Sarcoma of the Larynx Preceding Chronic Myeloid Leukemia

The authors report one case of granulocytic sarcoma infiltrating the larynx and cervical lymph nodes in a 50-year-old smoking patient. At the time of diagnosis there was no clinical and laboratory evidence of acute myeloid leukemia or chronic myeloproliferative disease. Four months after diagnosis, bone marrow morphology was consistent with chronic myeloid leukemia, accelerated phase. Cytogenetic abnormalities (Ph 1 chromosome, t(1; 12) (p36; p13), and trisomy of chromosome 20) were also found in hemopoetic cells. Granulocytic sarcoma preceding installation of chronic myeloid leukemia, as described here, seems to be a rare clinical event.

Chronic GVHD: predictive factor for rhinosinusitis in bone marrow transplantation

INTRODUCTION Bone marrow transplantation (BMT) is a treatment option for hematological diseases and immunodeficiency. It is frequently used today. BMT predisposes patients to upper airway infections and its complications, such as rhinosinusitis (RS). Chemotherapy, radiotherapy, viral infections, antibiotic therapy, graft versus host disease (GVHD) are rhinosinusitis predisposing conditions. AIM to investigate RS frequency in this population and its relationship to GVHD; to try and establish the best treatment for RS in these patients. METHOD ENT evaluation of two groups. One group with 35 patients (gI) and another with 24 patients (gII), before and after BMT. They were treated with antibiotics, maxillary sinus punction or endoscopic sinusectomy. RESULTS none of them had RS before BMT. 42.8% from gI had RS and 34% had GVHD; in the gII, 58% had RS and 25% had GVHD. 49% from both groups had RS and 30.5% had GVHD. There was significantly more RS in chronic GVHD patients. Surgery was used to treat RS in chronic GVHD patients who underwent BMT. CONCLUSION RS frequency was 49%; GVHD is a predisposing condition to RS; sinusectomy may be necessary to control RS in GVHD patients.

Associação entre HLA e leucemia em uma população brasileira de etnia mista

OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia). METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA). RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95%IC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95%IC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95%IC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95%IC = 1.34-4.16) was associated to increased risk of CML developing. CONCLUSION: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

DECH crônica: fator preditivo para rinossinusite no transplante de medula óssea

INTRODUCTION: Bone marrow transplantation (BMT) is a treatment option for hematological diseases and immunodeficiency. It is frequently used today. BMT predisposes patients to upper airway infections and its complications, such as rhinosinusitis (RS). Chemotherapy, radiotherapy, viral infections, antibiotic therapy, graft versus host disease (GVHD) are rhinosinusitis predisposing conditions. AIM: to investigate RS frequence in this population and its relationship to GVHD; to try and establish the best treatment for RS in these patients. METHOD: ENT evaluation of two groups. One group with 35 patients (gI) and another with 24 patients (gII), before and after BMT. They were treated with antibiotics, maxillary sinus punction or endoscopic sinusectomy. RESULTS: none of them had RS before BMT. 42.8% from gI had RS and 34% had GVHD; in the gII, 58% had RS and 25% had GVHD. 49% from both groups had RS and 30.5% had GVHD. There was significantly more RS in chronic GVHD patients. Surgery was used to treat RS in chronic GVHD patients who underwent BMT. CONCLUSION: RS frequence was 49%; GVHD is a predisposing condition to RS; sinusectomy may be necessary to control RS in GVHD patients.

Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR < or =4.5%. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.

Mobilization and collection of CD34+ cells for autologous transplantation of peripheral blood hematopoietic progenitor cells in children: analysis of two different granulocyte-colony stimulating factor doses

Introduction The use of peripheral hematopoietic progenitor cells (HPCs) is the cell choice in autologous transplantation. The classic dose of granulocyte-colony stimulating factor (G-CSF) for mobilization is a single daily dose of 10 μg/kg of patient body weight. There is a theory that higher doses of granulocyte-colony stimulating factor applied twice daily could increase the number of CD34+ cells collected in fewer leukapheresis procedures. Objective The aim of this study was to compare a fractionated dose of 15 μg G-CSF/kg of body weight and the conventional dose of granulocyte-colony stimulating factor in respect to the number of leukapheresis procedures required to achieve a minimum collection of 3 × 106 CD34+ cells/kg body weight. Methods Patients were divided into two groups: Group 10 – patients who received a single daily dose of 10 μg G-CSF/kg body weight and Group 15 – patients who received a fractioned dose of 15 μg G-CSF/kg body weight daily. The leukapheresis procedure was carried out in an automated cell separator. The autologous transplantation was carried out when a minimum number of 3 × 106 CD34+ cells/kg body weight was achieved. Results Group 10 comprised 39 patients and Group 15 comprised 26 patients. A total of 146 apheresis procedures were performed: 110 (75.3%) for Group 10 and 36 (24.7%) for Group 15. For Group 10, a median of three (range: 1–7) leukapheresis procedures and a mean of 8.89 × 106 CD34+ cells/kg body weight (±9.59) were collected whereas for Group 15 the corresponding values were one (range: 1–3) and 5.29 × 106 cells/kg body weight (±4.95). A statistically significant difference was found in relation to the number of apheresis procedures (p-value <0.0001). Conclusions To collect a minimum target of 3 × 106 CD34+ cells/kg body weight, the administration of a fractionated dose of 15 μg G-CSF/kg body weight significantly decreased the number of leukapheresis procedures performed.

Terapêutica citoprotetora em pacientes tratados com quimio e/ou radioterapia anti neoplásica

In recent years, cytoprotective agents have been developed to protect normal cells from the toxic effects of chemotherapy and radiotherapy. The ideal cytoprotectant is that which is able to allow intensification of chemotherapy; protects a broad spectrum of normal tissues and organs when used with a variety of chemotherapeutic agents; confers specific protection for normal tissues; preserves anti tumour activity and has little or manageable toxicity of its own. A cytoprotectant is administered prior to cytotoxic therapy, in contrast to the colony stimulant factors and Leucovorin, which are administered after chemotherapy to rescue the bone marrow and stimulate haematological recovery. Currently there are three cytoprotectors: two chemotherapy-specific (Dexrazoxane and Mesna) and one broad-spectrum (Amifostine). The authors discuss the main properties and usefulness of these drugs in Oncohematology.

Correlation of IL-6 and IL-10 production following bone marrow transplantation with donor cytokine gene polymorphisms

Estudos de varios genes candidatos tem demonstrado que polimorfismos geneticos em genes de citocinas contribuem com variacoes nos niveis de citocinas produzidas e esta variacao pode influenciar a ocorrencia e gravidade de complicacoes apos o transplante de celulas-tronco hematopoeticas (TCTH). Neste trabalho comparamos as concentracoes sericas de TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 em 13 receptores seguindo o TCTH com os polimorfismos TNF-308, IFNG+874, IL6-174, IL10-1082,-819,-592 e TGFB1+869,+915. Os niveis sericos de citocinas foram medidos usando-se kits comerciais de ELISA para TNF-α, IFN-γ, IL-6, IL-10 e TGF-β 1 (BioSource®, Nivelles, Belgium, Europe). Os genotipos de doadores/receptores para estes polimorfismos de citocinas foram analisados pela reacao em cadeia da polimerase com sequencias especificas de primer (PCR-SSP) com o kit Cytokine Genotyping Primers (One Lambda, Canoga Park, CA, USA). Encontramos correlacao entre os niveis de IL-6 e IL-10 seguindo o TCTH e os polimorfismos IL6-174 e IL10-1082,-819,-592, mas nao para outras citocinas investigadas neste estudo. Aqueles com genotipos relativos a baixa producao de IL-6 e IL-10 produziram mais baixos niveis destas citocinas que aqueles com genotipos relativos a producao alta e/ou intermediaria destas citocinas (P < 0,05).

Associação dos níveis de citocinas no pós-transplante de células-tronco hematopoiéticas com a Doença do Enxerto Contra o Hospedeiro aguda

This study was performed to investigate whether the serum levels of sIL-2R, TNF-alpha, IFN-gamma, IL-6, IL-10, and TGF-beta1 are associated with the development of acute GVHD. Serum cytokine levels were sequentially measured by sandwich Enzyme Linked-Immuno-Sorbent Assay (Elisa) in 13 patients who had received full match allogeneic stem cell transplantation. Serum sIL-2R and IL-10 levels from the 1st to the 15th week post transplantation were significantly higher in the group who developed acute GVHD than in the group without acute GVHD. Soluble IL-2R levels increased in direct correlation to engraftment and onset of acute GVHD, while IL-10 levels increased transiently following transplantation. The mean TNF-alpha concentration in the first weeks after transplantation was augmented in the group that developed acute GVHD. Furthermore, a drop in TGF-beta1 levels after the engraftment was significantly associated to acute GVHD. No correlation was found between acute GVHD and the other evaluated cytokines. These results support the idea that a balance between cytokines derived from type 1 and type 2 T-helper cells may be important in the development and control of acute GVHD. Although sIL-2R, TNF-alpha, IL-10, and TGF-beta1 levels, correlated with acute GVHD, sIL-2R levels at the engraftment may provide a better parameter for the early detection of acute GVHD after allogeneic stem cell transplantation.