外周血造血干细胞移植治疗恶性血液病53例

背景与目的:造血干细胞移植使恶性血液病的预后得到很大的改观,外周血造血干细胞移植(transplantation of peripheral blood stem cells,PBSCT)逐渐取代了骨髓移植(bone marrow transplantation,BMT)而成为造血干细胞移植的主要方式.本研究观察了自体或异基因外周血造血干细胞移植对53例恶性血液病患者的治疗效果.方法:53例恶性血液病患者于2003年7月～2006年5月在郑州大学第一附属医院血液科接受PBSCT治疗,中位年龄37岁.采用G-CSF或化疗联合G-CSF动员外周血干细胞.自体移植患者接受CD34 细胞的中位数为3.0×106/kg,异基因移植患者接受CD34 细胞的中位数为6.2×106/kg;自体移植采用MAC预处理方案,异基因移植采用改良的Bu/Cy预处理方案;移植物抗宿主病(graft versus host disease,GVHD)的预防采用MTX、环孢菌素A联合骁悉,1例1个点不合患者加用抗淋巴细胞球蛋白.结果:移植后中性粒细胞≥0.5×109/L、血小板≥20×109/L的天数在自体移植中分别为13天和19天,在异基因移植中分别为12天和15天;异基因移植中Ⅰ～Ⅲ度急性GVHD(aGVHD)的发生率为31.4%,慢性GVHD(cGVHD)的发生率为71.4%,复发率在自体移植和异基因移植患者中分别为38.9%和5.7%,700天无病生存率在自体移植和异基因移植患者中分别为57.9%和69.5%.结论:自体和异基因外周血造血干细胞移植均能很快地重建造血,是治疗恶性血液病的重要手段之一.     

Risk factors for severe radiation pneumonitis in lung cancer.

BACKGROUND: Risk factors for severe radiation pneumonitis, which often spreads beyond treatment portals and may even be bilateral, have not been fully investigated. The purpose of this study was to identify important factors associated with severe radiation pneumonitis. METHODS: 111 cases of primary lung cancer, treated with radiotherapy or chemoradiotherapy, were retrospectively analyzed. RESULTS: Severe radiation pneumonitis occurred in 17 cases (15.3%). The ratio of interstitial change in lungs before radiotherapy and radiotherapy to the contralateral mediastinum with > 40 Gy in the radiation pneumonitis group (RP group) was significantly higher than in patients without radiation pneumonitis (control group) (47.1% vs 5.3%; P < 0.001 and 58.8% vs 27.7%; P = 0.037, respectively). Using logistic regression analysis, interstitial changes before radiotherapy and radiotherapy to the contralateral mediastinum of > 40 Gy were significant risk factors associated with severe radiation pneumonitis. CONCLUSIONS: These data suggest that pre-existing interstitial changes detected by chest radiography or computed tomography and radiotherapy to the contralateral mediastinum (> 40 Gy) may predict the development of severe radiation pneumonitis.     

诱导aGVHD策略的异基因造血干细胞移植治疗难治复发性急性白血病的初步临床报告

背景与目的：异基因造血干细胞移植治疗难治复发性急性白血病,因移植后复发率和移植相关死亡率高而预后仍较差。本研究旨在探讨异基因造血干细胞移植治疗难治复发性急性白血病的过程中,主动诱导急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)对防止复发的作用。方法：30例成人难治复发性急性白血病,其中急性淋巴细胞白血病16例,急性非淋巴细胞白血病10例,混合性急性白血病4例。移植时第一次完全缓解4例,第二次完全缓解9例,部分缓解12例,未缓解5例。分别实施亲缘性同胞外周血干细胞移植24例(全相合者21例和不相合者3例),非亲缘性全相合移植6例(骨髓移植5例和外周血干细胞移植1例)。所有病例均接受清髓性预处理而强化清除残留白血病细胞的作用。亲缘性全相合者单用环孢素A,亲缘性不相合者或非亲缘性全相合者采取环孢素A 甲氨蝶呤 骁悉 小剂量ATG方法预防aGvHD。移植后 30至 60天仍无aGVHD者,采取每周20％～30％比例逐步减少环孢素A维持剂量及预制性供者淋巴细胞输注等方法诱导移植后早期aGVHD的发生。结果：移植后中位随访18．1月,aGVHD发生率80％(24／30),其中Ⅲ～Ⅳ度aGVHD发生率13．3％(4／30)。在可评价的19例患者中慢性移植物抗宿主病(cGVHD)发生率57．9％(11／19),其中广泛性cGVHD发生率15．8％(3／19)。移植后18例无病生存,无病生存率60％(18／30)。12例死亡,其中复发率17．9％(5／28)和移植相关死亡率23．3％(7／30)。结论：诱导aGVHD策略在防止难治复发性急性白血病移植后复发方面有一定作用。     

异基因造血干细胞移植治疗血液肿瘤5例

目的；探讨基因造血干细胞移植对血液肿瘤的疗效。方法：采用异基因造血干细胞移植治疗血液肿瘤５例，包括２例第一次完全缓解（ＣＲ１）急性粒细胞白血病，１例ＣＲ１急性淋巴细胞白血病，１例急性粒细胞白血产现任昨发和１例非霍奇金氏淋巴瘤Ⅳ期ＣＲ１。其中异基因骨髓移植４例，异基因外周血造血干细胞移植１例。所有病例均采用ＴＢＩ＋ＣＹ＋ＣＣＮＵ作预处理。结果：所有病例均移植成功。２例发生急性移植抗宿主病，２例发生慢     

Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

PURPOSE: We have used a nonmyeloablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy. PATIENTS AND METHODS: We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130). RESULTS: Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD; P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003). CONCLUSION: New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.     

Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin.

Purpose: With improved HLA-typing techniques, it is presently unclear what degree of identity is necessary for successful unrelated-donor stem-cell transplantation (UD SCT). Here, we describe the outcome after matched and mismatched UD SCT using a graft-versus-host disease (GVHD) prophylaxis including high-dose rabbit anti-T lymphocyte globulin (ATG). Patients and Methods: One hundred adult patients (median age, 37 years; range, 17 to 65 years) with hematologic malignancies underwent transplantation in early disease (first complete remission [CR1] or first chronic phase [CP1]; n = 34) or in advanced disease (second complete remission or second chronic phase, no remission, refractory; n = 66) with nondepleted bone marrow (n = 87) or peripheral-blood-derived (n = 13) stem cells from an HLA-A, HLA-B, HLA-DRB1*, or HLA-DQB1* identical (n = 75) or mismatched (one antigen, n = 21; two to three antigens, n = 4) unrelated donor. GVHD prophylaxis consisted of rabbit ATG before transplantation in addition to cyclosporine and short-course methotrexate. Results: The cumulative incidence of acute GVHD degrees II- degrees IV was 21% (95% confidence interval [CI], 14% to 33%) and 20% (95% CI, 9% to 44%) and acute GVHD degrees III- degrees IV was 5.3% (95% CI, 2% to 14%) and 4% (95% CI, 0.6% to 28%) in HLA-matched and HLA-mismatched transplantations, respectively. The risk for extensive chronic GVHD was 43% (95% CI, 32% to 59%) and 44% (95% CI, 26% to 75%) for HLA-matched and HLA-mismatched patients, respectively. The risk of relapse at 4 years was 17% (95% CI, 7% to 43%) and 43% (95% CI, 31% to 60%) for CR1/CP1 and advanced disease patients, respectively. With a median follow-up of 1,068 days (range, 12 to 1,958 days), 3-year disease-free and overall survival for patients who underwent transplantation in CR1/CP1 was 63% (95% CI, 46% to 81%) and 75% (95% CI, 59% to 90%), respectively; and for patients with advanced disease, it was 34% (95% CI, 22% to 46%) and 39% (95% CI, 25% to 53%), respectively. Conclusion: A certain degree of one antigen mismatching may not compromise the outcome after UD SCT when using this rabbit ATG in addition to standard GVHD prophylaxis regimen.     

Long-term follow-up of a phase I study of high-dose decitabine,busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias

BACKGROUND: Decitabine is a hypomethylating agent that has activity in patients with leukemia. The authors combined decitabine with busulfan and cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. METHODS: Patients with high-risk acute myeloid leukemia (AML) (n = 12 patients); chronic myelomonocytic leukemia (CMML) (n = 1 patient); acute lymphocytic leukemia (ALL) (n = 1 patient); or late chronic phase, accelerated, or blastic phase chronic myelogenous leukemia (n = 9 patients) were eligible for the study. The treatment plan was comprised of busulfan, 12 mg/kg orally; cyclophosphamide, 100 mg/kg (n = 4 patients) or 120 mg/kg (n = 19 patients); and decitabine, intravenously at 3 dose levels: 400 mg/m(2) (n = 10 patients), 600 mg/m(2) (n = 8 patients), and 800 mg/m(2) (n = 5 patients). Donors were human leukocyte antigen-identical siblings in all cases, and all but one patient received peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus based in all but one patient. RESULTS: The median time to neutrophil and platelet engraftment was 12.5 days and 17.5 days, respectively. Twenty-one patients were engrafted and achieved disease remission. At a median of 3.3 years posttransplantation, 26% of patients (40% of patients with AML) were alive and disease free. The median survival for the group was 17.2 months, and the disease free survival for the group was 8.9 months. Causes of death were disease recurrence (nine patients), chronic GVHD (four patients), infections (three patients), and acute GVHD (one patient). The 100-day mortality rate was 9%. No decitabine dose-limiting toxicity was documented. The treatment-related mortality rate at 3 years was 35%. Responders were treated at all three decitabine dose levels, and no dose-response correlation was observed. CONCLUSIONS: There was a high response rate with low treatment-related mortality, with 26% of patients alive in remission 3.3 years after transplantation.     

Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy in BT4C rat glioma model

Adenovirus (Adv)-mediated herpes simplex virus thymidine kinase (adv/tk) gene therapy combined with ganciclovir (GCV) medication is a promising approach for the treatment of malignant glioma. However, optimal administration and the effect of possible adjuvant treatments have not been fully examined. In the present study, we examined the efficacy of adv/tk/GCV gene therapy in a syngeneic BT4C rat malignant glioma model, either as a single administration or given as three injections during three consecutive days. The effect of combined adv-mediated macrophage colony-stimulating factor (MCSF) and adv/tk gene transfer was also studied. BT4C malignant glioma cells were injected into the right corpus callosum of BDIX rats (n=112). Before gene therapy, the presence of tumors was verified by MRI. The rats were divided into eight groups as follows: group I (n=20) received a single adv/tk gene transfer (total dose 4x10(8) pfu) and GCV treatment for 14 days; group II (n=5) received the same gene transfer without GCV; group III (n=28) received three adv/tk injections (total dose 4x10(8) pfu) on three consecutive days and GCV for 14 days; group IV (n=5) received three similar adv/tk injections without GCV medication; group V (n=13) received three adv/MCSF injections (total dose 2x10(8) pfu) on three consecutive days and GCV medication; group VI (n=12) received three adv/tk and adv/MCSF (total dose 6x10(8) pfu) injections on three consecutive days followed by GCV medication; and group VII (n=12) the same treatment without GCV. Group VIII (n=17) consisted of wild-type BT4C malignant glioma tumors without any treatment. Treatment effect and tissue responses were characterized by general histology, immunohistochemistry, MRI, and survival of the study groups. The best treatment effect and survival was found in rats treated with adv/tk gene transfer once a day for three consecutive days (P<.05). No improvement of the treatment effect was seen after the combined adv/tk and adv/MCSF gene transfer compared with the repeated adv/tk gene transfer. The results show that 20% of the rats can be cured (survival >6 months) after optimized adv/tk gene therapy. It is concluded that repeated intratumoral administration of adv/tk is a promising approach for the treatment of malignant glioma tumors in vivo.     

Allogeneic transplantation for patients with advanced acute leukemia: a single center retrospective study of 92 patients

Allogeneic transplantation is a well recognized treatment strategy of leukemia. However, its use in advanced leukemia patients is a subject of some debate especially when donors are not HLA-identical siblings because of the toxicity and cost of the procedure. We reviewed retrospectively the outcome of patients (pts) who received allogeneic transplantation for advanced acute leukemia in our center between 09/86 and 11/97. Thirty-six pts (study group) who lacked a matched sibling donor received partially matched related donor (n=14: PMRD group) or matched unrelated donor transplantation (n=22: MUD group). Fifteen pts had AML and 21 ALL. Seventeen pts (47%) were in CR>1, 13 pts (36%) had refractory disease and six pts (17.7%) were in untreated relapse. The outcome was compared to that of 56 patients (AML: 45.5 %, ALL: 55.5 %, CR>1: 49.9 %, refractory disease: 37.5 %, untreated relapse 19.6 %) who received allogeneic transplantation from a matched sibling donor (control group). Various conditioning regimens and GVHD prophylaxis were used. The actuarial incidence of grade II to IV acute GVHD was significantly higher in the study group (57%) than in the control group (34%) (p=0.047). The actuarial risk of relapse at three years was 21% +/- 22% in the study group versus 65% +/- 16% in the control group (p= 0.04). The actuarial probability of transplant-related mortality at 3 years is 64 +/- 16% for the study group and 25 +/- 11% for the control group (p=0.001). The leading cause of death in the study group was infection (30%) followed by acute GVHD and relapse. Relapse was the major cause of death in the control group (54%), followed by infection, interstitial pneumonia, veno-occlusive disease and GVHD. The OS and probability of leukemia-free survival at 3 years were 28 % +/- 15% (95% CI) and 27% +/- 15% (95% CI) in the study group. The overall survival and probability of LFS at 3 years were respectively 28 +/- 12% (95% CI) and 23 +/- 12% (95% CI) in the control group (p = 0.08 and p=0.11 respectively). In multivariate analysis, transplant-related mortality was higher in the study group (p=0.04) and lower if both donor and recipient were seronegative for CMV (p=0.007). OS was significantly higher for seronegative couples (p=0.0001), and when CR was achieved before BMT (p=0.0022). These results suggest that all efforts in this field should be directed on lowering the transplant related mortality for non geno-identical transplants and the relapse rate in geno-identical transplants.     

Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia.

PURPOSE: The purpose of this report was to review the Seattle experience in bone marrow transplantation (BMT) for acute myeloid leukemia (AML) during untreated first relapse. PATIENTS AND METHODS: Through 1990, 126 patients were transplanted during untreated first relapse of AML. Several preparative regimens were used, two of which involved more than 20 patients. Regimen 1 (29 patients) consisted of cyclophosphamide (CY) 120 mg/kg and 15.75 Gy of fractionated total-body irradiation (TBI) with methotrexate (MTX) given intermittently during a 102-day period to prevent graft-versus-host disease (GVHD). Regimen 2 (22 patients) consisted of the same CY and TBI treatment and a combination of MTX and cyclosporine (CSP) for GVHD prophylaxis. The remaining 75 patients were treated with 17 other transplant regimens. Outcome was compared for patients who were treated with regimen 1, regimen 2, and any other regimen. RESULTS: The 5-year probabilities of relapse-free survival (RFS), relapse, and nonrelapse mortality for 126 patients were .23, .57, and .44, respectively. With regimen 1, relapse (.26) was significantly less than for regimen 2 (.70; P = .004) or any other regimen (.76; P = .004). Regimen 1 patients developed more acute GVHD (.67) than regimen 2 patients (.26; P = .02) or patients on other regimens (.41; P = .02), and had increased nonrelapse mortality. Nevertheless, regimen 1 patients had a significantly higher 3-year RFS (.38) than those treated with regimen 2 (.18; P = .04) or any other regimen (.20; P = .05). CONCLUSIONS: For patients who received 120 mg/kg CY and 15.75 Gy TBI, relapse incidence was less and survival was better after GVHD prophylaxis with MTX alone than after a combination of MTX and CSP, despite a significantly higher incidence of acute GVHD. The results of treatment with regimen 1 justify future studies of the optimal timing of allogeneic BMT in the treatment of patients with AML.     

Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients: graft-versus-host disease and transplant-related mortality.

PURPOSE: To determine the risks of graft-versus-host disease (GVHD) and transplant-related mortality after allogeneic peripheral-blood stem-cell (PBSC) transplantation. PATIENTS AND METHODS: Between December 1994 and July 1996, 50 consecutive patients with high-risk hematologic malignancies in first remission or relapse received high-dose therapy followed by transplantation of granulocyte colony-stimulating factor-mobilized, allogeneic PBSCs collected from HLA-identical siblings. GVHD prophylaxis included cyclosporine and corticosteroids. RESULTS: As of April 1, 1998, 18 patients (36%+/-13%) survived with a median follow-up period of 767 days (range, 602 to 1,127 days). The actuarial probability of grades 2-4 acute GVHD was 0.37+/-0.14 (95% confidence interval). Of 36 assessable patients, 26 (72%+/-15%) developed chronic GVHD. The actuarial probability of chronic GVHD 2 years after transplantation was 0.87+/-0.15. Of 14 progression-free survivors, 11 (79%+/-22%) have active, chronic GVHD. All 11 patients require ongoing immunosuppression, and nearly two thirds have extensive disease. Thirteen patients died as a result of transplant-related mortality (26%+/-12%), six (12%) before and seven (14%) after day +100. CONCLUSION: We observed a high risk of chronic GVHD after allogeneic PBSC transplantation, which compromised the performance status of most long-term survivors and resulted in a relatively high risk of late transplant-related mortality. Approximately 75% of transplant-related deaths were associated with GVHD; thus, reduction in transplant-related mortality after allogeneic PBSC transplantation will require more effective strategies for the prophylaxis and/or treatment of GVHD.     

Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions.

In this prospective study we analyzed pre-emptive donor leukocyte infusions (DLI) in 82 consecutive patients transplanted with partially T cell-depleted grafts for acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, refractory anemia with excess of blasts, refractory anemia with excess of blasts in transformation and multiple myeloma. Donors were HLA-identical siblings. Patients without significant acute (>grade 1) and/or chronic GVHD were scheduled to be treated with DLI (35 patients) and 31 actually received DLI. Patients who developed acute GVHD >grade 1 and/or chronic GVHD were not scheduled to receive DLI and served as a comparison group (47 patients). The median interval between BMT and DLI was 22 weeks. The first six patients received 0.7 x 10(8) CD3+ cells/kg body weight (b.w.). Five out of these six patients developed acute GVHD (grade 1: n = 2, grade 3: n = 2 and grade 4: n= 1) which was more frequent and more severe than we had anticipated. In the next 25 patients the number of T lymphocytes was diminished to 0.1 x 10(8) CD3+ cells/kg b.w. which resulted in less frequent and less severe GVHD. Eight patients in this group developed acute GVHD (grade 1: n = 4, grade 2: n = 4) and three patients had limited chronic GVHD. Patients in the DLI group needed more time to establish complete donor chimerism confirmed by a higher number of mixed chimeras at 6 months after BMT. The projected 3-year probability of disease-free survival was 77% for the 35 patients intended to treat with DLI and 45% for the patients of the comparison group (P = 0.024). Relapse rate at 36 months after transplantation was 18% in the patients who were intended to treat with DLI and 44% in the comparison group (P = 0.026). We conclude that pre-emptive DLI is feasible and generates favorable relapse rates in patients who are at high risk for relapse. Furthermore, the incidence and severity of GVHD disease after DLI is dependent on the number of CD3+ cells infused.     

Allogeneic transplants with peripheral blood progenitor cells: a report of six cases

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 pg/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 14 times, more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 × 10⁹/L by day 12 to 21 post-transplant and a platelet count above 20 × 10⁹L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2). I (n = 1), II (n = 1), grade III (n = 1) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.     

非血缘造血干细胞移植中抗胸腺细胞球蛋白预防移植物抗宿主病的疗效分析

 【摘要】　  目的　探讨非血缘造血干细胞移植中应用抗胸腺细胞球蛋白（ATG）预防移植物抗宿主病（GVHD）的临床疗效。方法　回顾性分析1999年1月至2011年12月行非血缘造血干细胞移植患者治疗的恶性血液病（包括白血病、骨髓增生异常综合征、淋巴瘤）92例患者资料。分为ATG预防组（66例）和无ATG组（26例）。ATG剂量为1.5 mg／kg,移植前第4天至移植前第1天。比较两组急性GVHD（aGVHD）和慢性GVHD（cGVHD）发生率,分析aGVHD与cGVHD发生的危险因素,并比较ATG预防对移植后总生存（OS）、治疗相关死亡（TRM）率、复发率的影响。结果　Ⅱ～Ⅳ度aGVHD和Ⅲ～Ⅳ度aGVHD发生率差异无统计学意义[26.7 %（16／60）比44.0 %（11／25）,P＝0.12;13.3 %（8／60）比 8.0 %（2／25）,P＝0.74]。ATG组cGVHD及广泛型cGVHD发生率明显低于无ATG组[ 34.0 %（17／50）比 72.2 %（13／18）,P＝0.005;10.0 %（5／50）比44.4 %（8／18）,P＝0.005]。多因素分析显示ATG预防能降低cGVHD发生[相对危险度（RR）＝0.22,95 % CI 0.081～0.599;P＝0.003],人类白细胞抗原（HLA）不完全相合增加cGVDH发生率（RR＝3.25,95 % CI 1.39～7.61;P＝0.007）。并且ATG预防显著降低广泛型cGVHD发生（RR＝0.05,95 % CI 0.009～0.240;P＜0.001）。92例患者中位随访时间12个月（1～84个月）。ATG预防组和无ATG组间OS率（60.4 % 比43.1 %,P＝0.41）、TRM率（19.8 %比34.3 %,P＝0.43）、复发率（40.6 % 比33.6 %,P＝0.54）差异均无统计学意义。结论　总量6 mg／kg的ATG预防可显著降低非血缘造血干细胞移植患者cGVHD及广泛型cGVHD的发生率,不增加疾病复发,对OS及TRM亦无影响。     

Bone marrow transplantation for children with acute myelogenous leukaemia in the first complete remission

Of 52 children aged 9 months to 16 years old with acute myelogenous leukaemia (AML) in first complete remission undergoing bone marrow transplantation at our institution, 31 received allogeneic transplants (allo-BMT) and 21 received autologous transplants (ABMT). Initial induction and consolidation chemotherapy were not uniform. BMT was performed at a median of 7 months (range: 2.5 to 22.5 months) from the diagnosis. Conditioning included chemotherapy (n=43: 4 x 4 mg/kg of busulfan and 3 x 60 to 70 mg/m(2) of melphalan) or total body irradiation (12 Gy) plus chemotherapy (n=9). Graft-versus-host disease (GVHD) prophylaxis in allo-BMT cases consisted of methotrexate +/- cyclosporin A. Unpurged marrow was used in ABMT cases. All patients showed sustained engraftment. Amongst allograft cases, acute or chronic GVHD developed in 7 patients each (23%). 8 patients (15%) died (5 with allo-BMT, 3 with ABMT), including transplant-related mortality in 3 of the allo-BMT patients. 7 patients had relapses (3 with allo-BMT, 4 with ABMT). As of June 1999, 43 patients are alive and well 13 to 160 months after BMT (median, 71), with 5-year disease-free survival rates after BMT of 84% for allo-BMT, 81% for ABMT and 83% altogether. Although the presented data are based on a retrospective evaluation, we consider BMT for childhood AML during first complete remission an effective treatment for eradicating leukaemia.     

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. PATIENTS AND METHODS: The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). RESULTS: Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. CONCLUSION: Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.     

异基因外周血干细胞移植后外周血出现幼稚粒细胞与白血病复发的关系

目的了解异基因外周血干细胞移植（allo-PBSCT）后白血病复发与外周血幼稚粒细胞的关系。方法97例白血病患者经allo-PBSCT治疗,于14、30、60、90、120、180d及1年以后骨髓随访时同时观察外周血幼稚粒细胞出现情况,分析与白血病复发的关系。结果97例中,15例发生白血病复发。在30d及其以后外周出现幼稚粒细胞的57例中,复发14例,复发率24．6％,而30d及其以后外周血未出现幼稚粒细胞者的40例中仅有1例复发,复发率2．5％（P〈0．05）。复发与不复发者移植物抗宿主病（GVHD）差异无统计学薏：义（P〉0．05）。结论白血病复发与移植后外周血幼稚粒细胞有关．复发后治疗难度大,预后差。     

Interstitial pneumonitis

The risk management of interstitial pneumonitis in cancer chemotherapy not only involves an adverse event by an anticancer drug, but there are four steps with the incidence of interstitial pneumonitis: 1 ) the time before chemotherapy treatment, selection of chemotherapy regimens and patients, 2 ) the time chemotherapy treatment is performed, 3 ) the time during following-up, 4 ) the time when interstitial pneumonitis occurs. It is necessary to decrease the risk of interstitial pneumonitis by several steps, cooperating with an entire medical staff.     

The Use of Post-transplantation Cyclophosphamide in Peripheral Blood HLA-matched Stem Cell Transplantation as Graft-versus-host Disease Prophylaxis in Patients With Malignant or Non-malignant Hematologic Disorders: A Single-center Experience of 52 Patients

IntroductionStudies addressing the utilization of post-transplant cyclophosphamide (CY) as graft-versus-host disease (GVHD) prophylaxis in allogeneic hemopoietic stem cell transplantation from matched sibling donors are limited and with controversial results. Chronic GVHD incidence necessitating systemic treatment is around 35% in peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen-matched sibling donors.Patients and MethodsIn this study, high-dose CY was added to PBSCT aiming to reduce the incidence of GVHD to reach a lower figure compared with standard GVHD prophylaxis. Fifty-two patients with either benign or malignant hematologic disorders who underwent stem cell transplantation at Nasser Institute Hospital in Egypt from November 2017 to October 2018 were enrolled in this study. Fifty patients had fully human leukocyte antigen-matched siblings, whereas the remaining 2 patients had 1 locus class I mismatched donors. Pre-transplant conditioning regimen was fludarabine and busulfan (FLU/BU) in malignant cases (73.1%) and FLU/CY in benign hematologic disorders (26.9%) and 1 patient with hypocellular myelodysplastic syndrome. For GVHD prophylaxis, CY was given at a dose of 50 mg/kg/day on days 3 and 4 post-transplantation, and cyclosporine (CSA) starting day 5 in 96.1% of patients. For the 1-locus mismatched patients, both CSA and mycophenolate mofetil were administered starting day 5.ResultsThe 1-year incidence of acute GVHD (aGVHD) was 15.3% and for chronic GVHD (cGVHD) was 13.4%. Historical data of GVHD prophylaxis at our center using CSA and methotrexate showed an incidence of 37% for aGVHD and 33.9% for cGVHD.ConclusionsPost-transplant CY GVHD prophylaxis led to significantly less aGVHD (P = .03) and cGVHD (P = .04).     

Hyperfractionated total body irradiation for bone marrow transplantation: I. early results in leukemia patients

Bone marrow transplantation following cytoreduction with total body irradiation and cyclopbospbamide has previously been shown to be of value in treating refractory leukemias. Major problems, however, have been fatal interstitial pneumonitis and leukmmac relapse. In an attempt to minimize these problems, we initiated a new hyperfractionsted regimen for total body irradiation, with partial long sparing. From May, 1979 throughJuly, 1980, we treated 48 leukemia patients according to this regimen, varying in age from 1.5 to 42 years old (mead age: 18 y). Analysis in September, 1980, with follow-up from 2–16 mos, showed that we have a significantly reduced incidence of interstitial pneumonitis compared with single dose (1000 rad) irradiation (33 vs 70%), as well as decreased deaths attributable to interstitial pneumonitis (23 vs 50%). This is reflected in the survival curves, with loss of the early drop in survival previously observed with single dose irradiation. One year actuarial survival was 65% for acute lympbocytic leukemia (n - 16) and 72% for acute non-lymphocytic leukemia (n - 29). This compares with only 17% for acute non-lympbocytic leukemia patients (n = 12) on our previous single dose regimen. Age was: also found to be an important parameter for both survival and interstitial pneumonitis.