ISSN:0001-5792    

DOI:10.1159/000203867

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203868

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203869

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203870

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Allogeneic bone marrow transplantation is most commonly used as treatment for leukemia. Allotransplantation is associated with several interrelated immunologic processes, graft rejection, graft-versus-host disease (GvHD) and graft versus leukemia (GvL). Graft rejection can be overcome by intensive pretransplant immunosuppressive therapy. Following transplantation, immunoreconstitution must occur from donor-derived progenitors and GvHD may occur from reactivity of donor-derived immunocompetent cells against host tissues. In a related, but distinct process, donor immunocompetent cells may react against the recipient leukemia and recent data confirm that this GvL effect plays a critical role in preventing posttransplant relapse. This report summarizes present data regarding the mechanism of these processes. A major challenge is to separate the beneficial GvL effect from GvHD, the major complication of allogeneic marrow transplantation. We summarize data regarding innovative approaches to modify the composition of the transplanted marrow to optimize clinical outcome as well as use of donor lymphocyte infusions as a means to induce posttransplant GvL.

ISSN:0001-5792    

DOI:10.1159/000203871

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied the kinetic response and concentration of bone marrow (BM) progenitor cells of patients with lymphoid malignancies submitted to autologous bone marrow transplantation (ABMT), treated with a granulocyte-colony-stimulating factor (G-CSF)/interleukin-3 (IL-3) combination. The results were compared with those of lymphoma patients receiving the same pretransplant conditioning regimen followed by G-CSF alone. Recombinant human (rh)G-CSF was administered as a single subcutaneous (s.c.) injection at the dose of 5 μg/kg/day from day +1 after reinfusion of autologous stem cells, while rhIL-3 was added from day +6 at the dose of lOμg/kg/day s.c. (overlapping schedule). In both groups (i.e. G-CSF- and G-CSF/ IL-3-treated patients), cytokine administration was discontinued when the absolute neutrophil count was > 0.5 × 109/l of peripheral blood for 3 consecutive days. Following treatment with the CSF combination, the percentage of marrow CFU-GM and erythroid progenitors (BFU-E) in the S phase of the cell cycle increased from 9.3 ± 2 to 33.3 ± 12% and from 14.6 ± 3 to 35 ± 6%, respectively (p < 0.05). The number of actively cycling megakaryocyte progenitors (CFU-MK and BFU-MK) also increased. Conversely, G-CSF augmented the proliferative rate of CFU-GM (22.6 ± 6% compared to a baseline value of 11.5 ± 3%; p < 0.05) but not of BFU-E, CFU-MK or BFU-MK, and the increase in S-phase CFU-GM was significantly lower than that observed in the posttreatment samples of patients receiving IL-3 in addition to G-CSF. The absolute number of both CFU-GM and BFU-E/ml of BM was significantly augmented after treatment with G-CSF/IL-3 but not G-CSF alone. Similarly, administration of the cytokine combination resulted in a higher number of CD34+ cells and their concentration was significantly greater than that observed in the posttreatment samples of G-CSF patients. We also investigated the responsiveness to CSFs, in vitro, of highly enriched CD34+ cells, collected after priming with G-CSF in vivo (i.e. after 5 days of G-CSF administration). Our results demonstrated that pretreatment with G-CSF modified the response of BM cells to subsequent stimulation with additional CSFs. When the hematological reconstitution of patients treated with G-CSF/IL-3 was compared to that of individuals receiving G-CSF alone, the addition of IL-3 resulted in a significant improvement in granulocyte and platelet recovery, a lower transfusion requirement and shorted hospitalization. In conclusion, our results indicate that in vivo administration of two cytokines increases the proliferative rate and concentration of BM progenitor cells better than G-CSF alone and support a role for growth factor combinations for accelerating hematopoietic recovery after high-dose chem

ISSN:0001-5792    

DOI:10.1159/000203872

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The clonogenic capacity of human umbilical cord blood (UCB) has been evaluated in several studies, which have shown high numbers of primitive hematopoietic progenitor cells. Recently, UCB progenitor cells were demonstrated to possess significant advantages over bone marrow (BM) in terms of proliferative capacity and immunologic reactivity. Therefore, UCB has been considered an attractive source of hematopoietic stem cells for both research and clinical applications. Previous reports have documented a significant loss of progenitor cells by any manipulation other than cryopreservation. We have evaluated the feasibility of fractionating and cryopreserving UCB samples with minimal loss of progenitor cells. We compared separation over three different densities of Percoll (1.069, 1.077 and 1.084 g/ml), sedimentation over poligeline (Emagel), and sedimentation over poligeline followed by separation over Ficoll/Hypaque (F/H). Separated samples (n = 25) were analyzed for recovery of CD34+ cells and progenitor cells (CFU-GEMM, BFU-E, CFU-GM). Separation by sedimentation over poligeline followed by F/H allowed the highest depletion of RBCs (hematocrit of the final cellular suspension 0.4 ± 0.1%), while maintaining a high recovery of CD34+ cells (85.3%) and total recovery of CFU-GEMM, BFU-E and CFU-GM. After cryopreservation, recovery of clonogenic progenitors was 82% for CFU-GEMM, 94% for BFU-E, 82% for CFU-GM and 90% for colony-forming units after 5 weeks of long-term culture. Moreover, the presence of Stem cell factor significantly increased CFU-GEMM (14 ± 4 vs. 49 ± 5, p < 0.0005) and CFU-GM (112 ± 18 vs. 178 ± 19, p ≤ 0.025), but not BFU-E (42 ± 7 vs. 53 ± 7, p < 0.375) growth. In conclusion, RBC depletion of UCB can be accomplished with minimal loss of committed and primitive hematopoietic progenitors. This procedure may have important implications in the large-scale banking of UCB and in ex vivo expansion/gene therapy p

ISSN:0001-5792    

DOI:10.1159/000203873

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Peripheral blood precursor cells (PBPCs) are used with increasing frequency for hematopoietic transplants and have more or less replaced autologous bone marrow transplants. First clinical and experimental reports document the feasibility of PBPCs as a source for allogeneic transplants. Few data exist on the optimal procedure and the ideal number of cells for the transplant. We have previously shown in rabbits that PBPCs can be used for transplants even across a major histocompatibility barrier. We used this model to test whether the number of transplanted precursor cells would influence graft outcome. Adult outbred Red Burgundy rabbits were used as donors, New Zealand White rabbits of the opposite sex as recipients. One individual donor was taken for one individual recipient. Conditioning consisted of single-dose total body irradiation of 10 Gy followed by a short course of cyclosporine to enhance engraftment. Donor animals were treated with recombinant human granulocyte-colony-stimulating factor, 10 μg/kg subcutaneously daily from day -2 until day +9. PBPCs were obtained from the artery of the donor animal by repetitive centrifugation of 2 × 40 ml heparinized blood on each day of donation, i.e. days 0, +2, +3, +6, +8, and +10 and infused without further manipulation. Eight animals underwent transplantation. Seven took the grafts, six died of graft-versus-host disease and pneumonia between days 12 and 55 (median survival of all animals: 34 days). One animal was still alive after 120 days. Transplanted nucleated cells varied from 7.3 to 15.4 × 108/kg (median 9.2 × 108/kg) and CFU-GM from 12.3 to 176.8 × 104/kg (median 42 × 104/kg). Survival tended to increase with more CFU-GM) r = 0.716, p = 0.0704). These data confirm that allogeneic PBPCs can engraft across a major histocompatibility barrier and suggest that a higher number of CFU-GM might be advanta

ISSN:0001-5792    

DOI:10.1159/000203874

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We review the problem of lymphoma classification in the light of the Revised European-American Lymphoma (REAL) scheme, recently proposed by the International Lymphoma Study Group (ILSG). The REAL classification is a list of clinicopathologic entities, all well known from the literature, upon which the ILSG members agreed. Although it contains nothing new, for the first time all the elements, including immunophenotype and molecular data, which characterise a given lymphoma entity are considered. This approach corresponds to the need for objective criteria integrating the often puzzling morphologic findings. Furthermore, better knowledge of the molecular events which contribute to tumour development and progression is of paramount importance for the development of more specific and successful therapies. Some relevant molecular findings included in the classification and additional data obtained by the ILSG members following its publication are discussed.

ISSN:0001-5792    

DOI:10.1159/000203875

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In acute myelogenous leukemia, early treatment is usually attempted with the so-called 3+7 regimen, employing daunorubicin (DNR) or idarubicin (IDR) for 3 consecutive days. In acute lymphoblastic leukemia (ALL), the role of anthracyclines (ANTs) is less clearly defined, and there is a substantial lack of agreement regarding ANT dosage and schedule, preferable compound, and indications for remission induction and consolidation treatment phases. Here we review the role of these drugs in adult ALL. The results indicate that ANTs may offer the best survival chance when used at full dosage during induction and early consolidation treatment. IDR may be a better choice than DNR or doxorubicin, and CD10+ t(9;22)/bcr- ALL may have an excellent prognosis following an early dose-intensive ANT consolidation program.

ISSN:0001-5792    

DOI:10.1159/000203876

出版商:S. Karger AG    

年代:1996

数据来源: Karger