RESUMO
The optimal protocol for mobilization of hematopoietic stem cells in patients with lymphoid malignancies has not been determined so far. We retrospectively analyzed the efficacy and safety of Ara-C at a dose of 1.6 g/m(2) compared with CY at a dose of 4.0 g/m(2), both combined with filgrastim. Seventy and forty-five patients, respectively, were included, among whom 60% were defined as 'predicted poor mobilizers'. The use of Ara-C was associated with significantly higher peak number of circulating CD34(+) cells compared with CY (P<0.0001). In the Ara-C group, 95% of patients with multiple myeloma (MM) collected at least 5 × 10(6) CD34(+) cells/kg required for tandem transplantation, and 97% of lymphoma patients collected at least 2 × 10(6) CD34(+) cells/kg, needed for a single autologous hematopoietic SCT (autoHSCT), which was achieved with a single leukapheresis in 91% of cases. Results for the CY group were significantly inferior (P<0.0001). No patient mobilized with Ara-C experienced febrile neutropenia, whereas 35% required platelet transfusions. Among patients who proceeded to autoHSCT, the time of both neutrophil and platelet recovery was significantly shorter for those mobilized with Ara-C than CY. We conclude that intermediate-dose Ara-C+filgrastim is a very effective and relatively safe mobilization protocol for patients with lymphoid malignancies.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Mieloma Múltiplo/terapia , Adulto , Idoso , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/terapia , Transfusão de Plaquetas , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: The procedure of autologous hematopoietic stem/progenitor cell transplantation requires cryopreservation. Addition of DMSO is necessary to secure the viability of such cells, but this solvent is potentially toxic to stem cells' recipient. 10% DMSO solution is used by the majority of transplant centres. The aim of our study was to test if DMSO concentration might be reduced without negative impact on cell recovery and clonogenicity. MATERIALS AND METHODS: Samples were prospectively collected from 20 patients. Small volumes of leukapheresis products were frozen with different cryoprotective mixtures, containing 10%, 7·5%, 5% and 2·5% DMSO, respectively. The quality of cryoprotective mixtures was evaluated based on recovery, viability and clonogenic potential of hematopoietic stem cells after defreezing. RESULTS: Reduction in DMSO concentration to 7·5% or lower was associated with decreased recovery of nucleated cells. In contrast, the number of colonies was highest for 7·5% DMSO with significant differences when compared to 10% DMSO solution. CONCLUSION: Reduction in DMSO concentration from 10% to 7·5% may have favourable impact on hematopoietic recovery after autologous transplantation. The findings require confirmation in a clinical setting.
Assuntos
Criopreservação/métodos , Dimetil Sulfóxido/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco/citologia , Adulto , Idoso , Antígenos CD34/metabolismo , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Crioprotetores/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Leucaférese/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T/citologiaRESUMO
An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 × 14 g/m(2) treosulfan and 5 × 30 mg/m(2) fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for non-relapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III-IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II-IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/cirurgia , Condicionamento Pré-Transplante/métodos , Adulto , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/análogos & derivados , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Adulto JovemRESUMO
It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.
Assuntos
Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Transplante Homólogo , Adolescente , Adulto , Benzamidas , Bilirrubina/sangue , Plaquetas/metabolismo , Creatinina/sangue , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Quimeras de Transplante , Condicionamento Pré-Transplante/métodosRESUMO
We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.
Assuntos
Leucemia/terapia , Transplante de Células-Tronco , Antígenos CD/sangue , Antígenos CD34/sangue , Complexo CD3/sangue , Feminino , Humanos , Separação Imunomagnética , Terapia de Imunossupressão/métodos , Doadores Vivos/estatística & dados numéricos , Masculino , Irmãos , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
Assuntos
Transplante de Medula Óssea , Adulto , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença de Hodgkin/terapia , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/terapia , Metotrexato/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Transplante Autólogo , Transplante HomólogoAssuntos
Transplante de Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Transplante de Medula Óssea/fisiologia , Intervalo Livre de Doença , Eritropoese , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/fisiologia , Contagem de Plaquetas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Probabilidade , Taxa de Sobrevida , Fatores de Tempo , Transplante AutólogoRESUMO
Therapeutic results are described obtained with the preparation Dorsiflex produced by the Yugoslav institution Lek Ljubliana. The drug was given to 40 children aged 8 to 14 years with various neurological diseases with muscle hypertonus as the prevailing sign. The preparation was found to exert a good myorelaxant effect, facilitating comprehensive rehabilitation in cases in infantile cerebral palsy, after craniocerebral injuries, encephalomeningitis, degenerative diseases and other conditions. The drug was well tolerated.