ABSTRACT
There were 417 scientific articles on hematopoietic stem cell transplantation in the 54th annual meeting of American Society of Hematology (ASH),including 46 articles on lymphoma.This article reviews latest research on non-myeloablative allogeneic hematopoietic stem cell transplantation for the treatment non-Hodgkin' s lymphoma presented in the meeting.
ABSTRACT
Objective To study the reconstitution of nature kill cell early after non-myeloablative allogeneic stem cell transplantation (NAST). Methods Cell phenotypes and in vitro immune functions were analyzed by direct immune fluorescence with FCM, T-cell activation test and MTT assay, respectively. Results The percentages of CD+3, CD+4 cells were low, (2.03±15.60) % and (22.69±12.29)%, respectively, while CD+8 lymphocytes were normal or high [(29.26±8.99)%] 1 month after NAST. Proliferative response to a T lymphocyte activator (PHA) was blunted, 94.60±44.87. The percentage of NK cells was within normal limits or high (n=7) in allotransplanted patients. It is (18.77±9.11) %. The percentage of CD+56 NK cells expressing IL-2R (CD25) was high and values obtained from transplanted patients were significantly different from control values . They are (3.71±2.23) % (t = 2.116, P = 0.044). NK cell activity in part of patients was higher than that observed in control cells (25.30±12.39) % vs (16.60±3.53) % (t = 2.135, P= 0.047). Conclusion NK cell has recovered early after transplantation and may be particularly relevant as a first line of defence in immunosurveillance against neoplastic cells or microbial infections, until a full reconstitution of T cellmediated immune response can be achieved.
ABSTRACT
Objective To determine the safety and the therapeutic efficacy of autolagous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly-onset type 1 diabetes mellitus patients. Methods Fifteen patients with type 1 diabetes mellitus were enrolled. Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide and rabbit antithymocyte globulin. Serum levels of HbA1c, C-peptide levels, and anti-glutamic acid decarboxylase antibody (GAD-Ab)titers were measured before and after AHST. Meanwhile, adverse event was recorded.Results The average age of 18 patients (6 males and 12 females)was ( 18.8±4.4 )years, the mean follow-up was ( 414± 150 ) days. 67 % ( 12/18 ) patients became insulin free, the earliest one happened at 2 weeks after AHST, and the latest one at 6 months. 4 cases resumed insulin use because of influenza and other reasons resulting in the rise of blood glucose level. Currently, 8 patients (44.4%) were completely free of insulin therapy, and the remaining cases reduced the insulin dosage by 67.3% ±22.4%. 18 cases had lowered GAD-Ab level, the negative rate was 33.3% (6/18 ). Fasting and postprandial 2 h C-peptide levels increased significantly after A HST. Area under the curve for C-peptide ( AUCC ) increased much more markedly, and it could be maintained for 1 year. Duringtransplantation,all patients had varying degrees of gastrointestinal reactions, hair loss, fever, bone marrow suppression, and other side effects. 5 patients received blood component transfusion. No damage or other severe adverse events of heart, liver, kidney, and other organs were observed. Most side effects gradually disappeared after 2-4 weeks. The recovery of neutropenia was the slowest. Conclusion Autologous hematopoietic stem cell transplantation for treatment of newly-onset type 1 diabetes with residual islet function showed a certain effect and high safety. The widened use of this new technique should be cautious until the therapeutic mechanism has been further studied.
ABSTRACT
Objective To observe the efficacy and acute toxicity in non-myeloablative low-dose tatal body irradiation. Methods From January 2006 to January 2008, 27 cases of hematopoietic stem cell transplantation patients received non-myeloablative pretreatment program involving low-dose whole body irradiation. Pretreatment program: the total dose of TBI was 2 Gy, once completely. According to primary disease, physical condition, age, organ function and HAL coincide situation, the patients received different chemotherapy, including FUL, CTX, Ara-C, melphalan and so on. To prevent the graft-versus-host disease (GVHD), CSA/MMF was used. Results Hematopeietic reconstruction: the peripheral blood WBC in all 27 cases reduced to (0.05-0.9) × 109/L in 4 to 8 days, with the neutrophil count > 0.5 × 109/L in 8 to 22 days (median + 10.5 days), the platelet count > 30 × 109/L in 11 to 28 days (median + 14.5 days). The transplant rate was 85.2% (23/27). The fever rate was 65% and the infection rate was 37% (10/27). Hemorrhagic cystitis,hepatic veno-occlusive disease (HVOD), and other complications did not occurred. 4 cases developed aGVHD (15 %) and 5 cases developed cGVHD (19 %) out of 27 cases. Follow-up 3 to 22 months, 21 eases are still alive (77.8%). Conclusions Pretreatment with low-dose whole body irradiation of non-myeloablative hematopeietic stem cell transplantation proved to be simple and safe with fewer complications and broad indications. Program of TBI with total dose of 2 Gy (once completely) is a safe, less toxic and effective method. It could achieve the effectiveness of immune suppression.
ABSTRACT
Nonmyeloablative stem cell transplantation (NST) is increasingly used with beneficial effects because it can be applied to older patients with hematological malignancies and those with various complications who are not suitable for conventional myeloablative stem cell transplantation (CST). Various conditioning regimens differ in their myeloablative and immunosuppressive intensity. Regardless of the type of conditioning regimen, graft-versus- host disease (GVHD) in NST occurs almost equally in CST, although a slightly delayed development of acute GVHD is observed in NST. Although graft-versus-hematological malignancy effects (i.e., graft-versus-leukemia effect, graft-versus-lymphoma effect, and graft-versus-myeloma effect) also occur in NST, completely eradicating residual malignant cells through allogeneic immune responses is insufficient in cases with rapidly growing disease or uncontrolled progressive disease. Donor lymphocyte infusion (DLI) is sometimes combined to support engraftment and to augment the graft-versus-hematological malignancy effect, such as the graft-versus-leukemia effect. DLI is especially effective for controlling relapse in the chronic phase of chronic myelogenous leukemia, but not so effective against other diseases. Indeed, NST is a beneficial procedure for expanding the opportunity of allogeneic hematopoietic stem cell transplantation to many patients with hematological malignancies. However, a more sophisticated improvement in separating graft-versus-hematological malignancy effects from GVHD is required in the future.
Subject(s)
Humans , Antigen-Presenting Cells/physiology , Graft vs Host Disease/etiology , Graft vs Leukemia Effect , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia/therapy , Lymphocyte Transfusion , Lymphoma, Non-Hodgkin/therapy , Multiple Myeloma/therapy , Transplantation ConditioningABSTRACT
Objective: To evaluate the safety and efficacy of nonmyeloablative preconditioning allogeneic hematopoietic stem cell transplantation (NMHSCT) in the therapy of unidentified relapse and primary solid tu-mors, and to study the anti-tumor immunity induced by the effect of Graft-Verus-Tumor (GVT). Methods: A to-tal of 13 difficult-to-treat cancer patients received NMSCT and the efficacy and side effects were observed. Re-sults: One case had CR, 2 cases had PR, 4 cases had SD, 5 cases had PD, and 1 case died of complica-tions associated with transplantation. One case was GVT (+++), 3 cases were GVT (++), 5 cases were GVT(+), and 4 cases were GVT (-). The main side effect was acute GVHD presented as diarrhea and infec-tion. VOD and brain disease were rare. Conclusion: Nonmyeloablative allogeneic stem cell transplantation is safe and effective for solide tumors.
ABSTRACT
BACKGROUND: Although engraftment following murine allogeneic bone marrow transplantation (BMT) is most commonly confirmed by H2 typing using flow cytometry, recipient mice can be seriously injured during peripheral blood (PB) sampling. Therefore, we developed an alternative DNA-based assay that does not require the large volume of PB necessary for flow cytometry. METHODS: A minute volume of PB from the tail vein was used to evaluate the engraftment by PCR amplification of a microsatellite in the class II Eb gene. Dilution experiments were performed to evaluate the sensitivity of this assay for detecting donor cells in mixed cell populations compared with flow cytometry analysis. RESULTS: Early engraftment and mixed chimerism were confirmed, based on the length variation of the microsatellite in the class II Eb gene. The degree of donor chimerism in the donor-recipient cell mixture could be estimated semiquantitatively in a dilution experiment. The sensitivity of this assay by the naked eye approached 10% of the degree of donor chimerism. CONCLUSION: PCR amplification of a microsatellite in the class II Eb gene can be a useful alternative to flow cytometry for evaluating early engraftment and mixed chimerism following murine nonmyeloablative BMT.
Subject(s)
Animals , Humans , Mice , Bone Marrow Transplantation , Bone Marrow , Chimerism , Flow Cytometry , Microsatellite Repeats , Polymerase Chain Reaction , Tissue Donors , VeinsABSTRACT
BACKGROUND: The ability of non-myeloablative allogeneic stem cell transplants to eradicate host neoplastic cells is based on the accumulating evidence of a graft-versus-malignancy (GVM) effect. Stable mixed chimerism (MC) is associated to the lower risk for the development of graft-versus-host diseases (GVHD), but this possibly occurs at the expense of the GVM effect. Therefore, assessment of the chimerism status is critical to allow immune intervention to maintain a state of donor-host tolerance and to prevent loss of the graft. METHODS: Serial post-transplant peripheral blood samples were collected from 17 patients with various malignant diseases following non-myeloablative allogeneic stem cell transplantation. DNA was amplified from the T-cells, and the polymerase chain reaction (PCR) products were quantified by an automated fluorescent DNA analyzer. RESULTS: All 17 patients showed T-cell MC at post-transplant, but this varied in degree and duration, and then 3 patterns emerged. Group 1: 5 patients experienced a short interval of T-cell MC prior to conversion to complete donor chimerism (CC) (median: 25 days). Group 2: 5 patients showed a rapid increase of host cells after a brief MC at a median of 21 days. They never achieved CC, and they relapsed or showed progressive diseases. Group 3: 7 patients showed persistent T-cell MC for 40-50 days, and they subsequently gradually converted to CC after a median of 112 days. CONCLUSION: All the patients achieved T-cell MC in post-transplant, but the CC development differed in frequency and speed. GVHD preceded the onset of T-cell CC in the majority of the patients. Serial engraftment monitoring of the T-cell chimerism status during the first 100 days after non-myeloablative stem cell transplantation is important in aiding the clinical management of such patients.
Subject(s)
Humans , Chimerism , DNA , Graft vs Host Disease , Polymerase Chain Reaction , Stem Cell Transplantation , Stem Cells , T-Lymphocytes , Tissue Donors , TransplantsABSTRACT
BACKGROUND: The use of non-myeloablative stem cell transplantation (NST) has recently been increasing for treating the patients who cannot tolerate ablative hematopoietic stem cell transplantation (HSCT). Although graft-versus-host disease (GVHD) is one of the greatest problems in HSCT, the clinical effect of GVHD following NST is not clear. We undertook this study to evaluate the clinical manifestations of GVHD and the outcomes after NST. METHODS: From October 2000 to October 2004, 61 patients underwent NST with a fludarabine-based conditioning regimen. The cumulative incidence of GVHD and the survival rates were obtained from the Kaplan-Meier curves. RESULTS: With a median follow-up of 195 days, the estimate for overall three-year survival was 32%. The cumulative incidences of grades II~IV acute GVHD and chronic GVHD were 33% (18/53) and 78% (29/37), respectively. The response rates for acute and chronic GVHD were 33% and 89%, respectively. The survival rates of patients with acute and chronic GVHD were 27% and 89%, respectively. The median survival time was 6.5 months CONCLUSION: The incidence of GVHD after NST did not differ from that after ablative HSCT. This study suggests that the aggressive treatment of acute GVHD should be considered to improve the overall survival after NST.
Subject(s)
Humans , Follow-Up Studies , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Incidence , Stem Cell Transplantation , Survival RateABSTRACT
Based on the practive of traditional allogeneic hematopoietic stem-cell transplantation therapy allo-HSCT and the development of nonmyeloablative conditioning, a new immunotherapy for solid tumor nonmyeloablative allo-HSCT, has been initiated. The nonmyeloablative,preparative regimens are associated with the use of lower dose of drugs,and less treatment-related toxicities. Instead of achieving maximal tumor reduction, the regimens are disigned to induce adequate immunosuppression to permit the engraftment of donor hematopoietic stem cells and serve as the platform for the administration of donor T cell in adoptive cell therapy. Donor's T-cell mediates a graft-versus-tumor(GVT)effect. This response is effective for the eradication of acceptor's tumor cell. This article reviews the concept, rationale, early clinical results, and limitation of nonmyeloablative allo-HSCT as a novel immunotherapy in solid tumors.
ABSTRACT
A 31-year-old man presented fatigue, polydipsia and polyuria. He was diagnosed as acute myelogenous leukemia (AML) FAB-M1, and a water deprivation test confirmed central diabetes insipidus (DI). A sella magnetic resonance imaging showed the thickening of pituitary stalk with contrast enhancement suggesting leukemic infiltration. He was treated with remission induction chemotherapy including cytosine arabinoside and idarubicin, and concurrent intrathecal methotrexate, cytosine arabinoside and hydrocortisone. But he was not achieved a remission. Reinduction chemotherapy was also failed to induce remission. He underwent a non-myeloablative allogeneic he matopoietic stem cell transplantation (NST) from HLA one antigen mismatched sibling donor for refractory AML. After transplantation, he had no evidence of leukemia and DI, He showed complete conversion of donor chimerism. By day 7 after NST, desmopressin (DDAVP) was no longer required and a follow-up at 9 months he has no evidence of relapse. We report a rare case recovered from diabetes insipidus associated with acute myelogenous leukemia after NST in Korea.
Subject(s)
Adult , Humans , Chimerism , Cytarabine , Deamino Arginine Vasopressin , Diabetes Insipidus , Diabetes Insipidus, Neurogenic , Drug Therapy , Fatigue , Follow-Up Studies , Hydrocortisone , Idarubicin , Korea , Leukemia , Leukemia, Myeloid, Acute , Leukemic Infiltration , Magnetic Resonance Imaging , Methotrexate , Pituitary Gland , Polydipsia , Polyuria , Recurrence , Remission Induction , Siblings , Stem Cell Transplantation , Stem Cells , Tissue Donors , Water DeprivationABSTRACT
Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. so, Conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. however, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to developed. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.
Subject(s)
Aged , Humans , Chemoradiotherapy , Comorbidity , Drug Therapy , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Mortality , Radiotherapy , Stem Cell Transplantation , Stem CellsABSTRACT
Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. so, Conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. however, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to developed. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.
Subject(s)
Aged , Humans , Chemoradiotherapy , Comorbidity , Drug Therapy , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Mortality , Radiotherapy , Stem Cell Transplantation , Stem CellsABSTRACT
The purpose of this study was to investigate the clinical efficacy against acute leukemia by transplantation of nonmyeloablative allogeneic peripheral blood stem cells from unrelated donor (URD NAPBSCT). One patient with acute lymphoblastic leukemia received URD NAPBSCT in our hospital. The donor cells were full engafted, and grade Ⅱ skin aGVHD and interstitial pneumonia were developed. The results showed that URD NAPBSCT is an effective new method for the treatment of acute leukemia.
ABSTRACT
To explore the risk factors of graft rejection in non-myeloablative transplantation between HLA-identical siblings and to evaluate methods to increase donor cell engraftment, 8 patients with graft rejection were studied . The results showed that the usage of immunosup-pressive agents, low early engraft rate, and the kind of disease being CML were closely related with graft rejectioa For patients with graft rejection, second non-myeloablative transplantation is a useful way.
ABSTRACT
Objective To evaluate the efficacy and complications of nonmyeloablative stem cell transplantation(NST) for the treatment of nonmalignant haematologic diseases with high-risk rejection.Methods NST was performed for two patients with severe aplastic anemia(SAA) and one with beta-thalassemia major(TM).The protocal was designed on transplantation of granulocyte colony-stimulating factor(G-CSF) primed allogeneic bone marrow cells combined with perpheral blood stem cells(PBSCs) for two SAA patients,with conditioning regimen based on anti-lymphocyte globulin and reduced dose of cyclophosphamide(CTX).One TM patient was performed transplantation of PBSCs with conditioning regimen of anti-T-lymphocyte globulin(ATG),fludarabine and reduced dose of busulfan.Cyclosporin A combined with methylprednisone was used for graft-versus-host disease(GVHD) prophylaxis.Donor stem cells infusion(DSI) were underwent for three patients at 78,99 and 44 days post transplant respectively.Results Three patients achieved engraftment successfully with mixed chimera and the lowest white blood cell(WBC) of 0.26?10~9/L,0.5?10~9/L and 1.26?10~9/L respectively.The absolute neutrophil count achieved more than 0.5?10~9/L and platelet count achieved more than 20?10~9/L at days of 12d,3d,0d and 1d,5d,0d post transplant in three patients,respectively.The haematopoiesis and chimera were improved after DSI without complications of infection and GVHD in three patients.Conclusion The stem cells engraftment is achieved successfully with donor stem cell infusion followed NST for the treatment of nonmalignant haematologic disease patients with high-risk rejection.
ABSTRACT
To evaluate the effects of donor stem cell infusion (DSI) in patients after nonmyeloablative allogeneic peripheral blood stem cell transplantation( NAPBSCT),6 patients were infused donor stem cell in+7d～+90d consisting of MNC (0.6～7.6)?10 8 /kg, CD34 + cells (0.3～3.4)?10 6 /kg,CD3 + cells (0.3～5.1)?10 8 /kg.The results showed that 5/6 patients had definite effects in promoting donor chimeras after DSI,of these 3 achieved full donor chimeras following mixed chimeras ;4/6 have graft versus leukemia(GVL)effects.No hematopoiesis aplasia was found, and only one Ⅳdegree aGVHD developed related with DSI. It was concluded that DSI have definite GVL effects and can convert mixed chimeras to full chimeras without causing GVHD and severe hematopoietic aplasia.
ABSTRACT
This paper investigate the methods to detect engraftment rate of the four patients with hematological disorders who accepted nonmyeloablative allogeneic peripheral blood stem cell transplantation(NAPBSCT). To find out the best method, their engraftment rates were detected serially at different time after NAPBSCT by means of either FISH, or conventional chromosome analysis combined with R banding analysis concurrently.The results were carefully compared with one another. All these four sex mismatched cases were engrafted partially,and two of them changed to full engrafment. The results show no statistically significant difference in 3 groups (conventional method, FISH for hypermetaphase, FISH for interphase nuclei). But the results strongly indicate that FISH is a rapid, precise, objective,and reliable menthod for detection of the engraftment rate,and it is suitable for sex mismatched NAPBSCT.