Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: the experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.

Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant

Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34 percent) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.

Splenic and portal vein thrombosis following laparoscopic splenectomy in a pediatric patient with chronic myeloid leukemia

CONTEXT: Splenic or portal vein thrombosis is a rare complication following splenectomy. CASE REPORT: We report a case of splenic and portal venous thrombosis in a 10-year-old girl with chronic myeloid leukemia who underwent laparoscopic splenectomy prior to bone marrow transplant. Clinical suspicion of such thrombosis should be high for patients who have had splenectomy. The diagnosis is confirmed by Doppler ultrasound or contrast-enhanced computed tomography; magnetic resonance imaging magnetic resonance angiography or arteriography can also be used. Proposals for postoperative screening protocols are discussed. Patients with primary myeloproliferative disorders are at increased risk of portal vein thrombosis, independent of surgical intervention, perhaps due to platelet dysfunction resulting from abnormalities of pluripotent stem cells. Marked splenomegaly (with larger draining veins) is thought to increase the risk of thrombosis.

CONTEXTO: Trombose em veia portal ou esplênica é uma complicação rara pós-esplenectomia. RELATO DE CASO: Descrevemos um caso de trombose venosa portal e esplênica em uma menina de 10 anos de idade com leucemia mielóide crônica, a qual foi submetida a uma esplenectomia laparoscópica antes de um transplante de medula óssea. A suspeita clínica de tal trombose deve ser alta em pacientes que sofreram esplenectomia, e o diagnóstico é confirmado pelo ultra-som Doppler. Tomografia com contraste, ressonância magnética, angioressonância ou arteriografia podem também ser utilizados. Proposta de protocolo pós-operatório para avaliação de trombose é discutida.

Extensive chronic graft-versus-host disease of skin successfully treated with thalidomide.

Thirty years female underwent allogenic peripheral blood stem cell transplantation for chronic myeloid leukaemia--chronic phase. She developed grade II acute skin graft-versus-host disease (GVHD) which was treated with cyclosporine and a short course of steroids. She developed extensive chronic GVHD of the skin and liver three hundred days post-transplant. She was managed with the standard immunosuppressants with partial response of liver dysfunction but no response of skin lesions. She showed a good response to therapy with resolution of skin lesions after treatment with thalidomide.

Probability prediction in multistate survival models for patients with chronic myeloid leukaemia / 华中科技大学学报（医学）（英德文版）

In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis. After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse, especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or after relapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

O transplante de medula óssea alogênico de curto período de internação / Outpatient allogeneic bone marrow transplantation

Foram analisados os resultados retrospectivos do transplante de medula óssea alogênico em 100 pacientes portadores de leucemia mielóide crônica, divididos em dois grupos: Grupo I, de 49 pacientes que recebeu alta hospitalar após a pega medular, e grupo II, de 51 pacientes, que recebeu alta precocemente, antes da pega medular, para acompanhamento ambulatorial. Foram comparados os dias de ocupação de leitos hospitalares, a morbidade e a mortalidade entre os grupos de alta até o dia 100 pós transplante. /We analyzed the results of a retrospective study of 100 patients with chronic myelogenous leukemia submitted to allogeneic stem cell transplantation in one of two settings: Group I, with 49 patients, transplanted in the traditional inpatient and group II, with 51 patients, in partial outpatient. We compared the median number of days spent in hospital, morbidity and mortality within 100 after bone marrow transplantation. We concluded that there was a significant reduction in the median of hospital length of stay in the partial outpatient group, without increasing morbidity and mortality...