Autologous bone marrow transplantation in hematologic malignancies

Autologous bone marrow transplantation (BMT) has become effective therapy for high-risk hematologic leukemias with long-term disease-free survivals and apparent cure in a substantial fraction of patients with relapsed aggressive non-Hodgkin's lymphoma, relapsed Hodgkin's disease, and the acute leukemias. Preliminary reports suggest autologous BMT may also be useful treatment for low-grade non-Hodgkin's lymphomas, chronic myelogenous leukemia, and multiple myeloma. Recent studies have begun to address the role autologous BMT should play in these diseases, especially relative to conventional-dose therapy and allogeneic BMT. Relapse remains the major cause for failure following autologous BMT. Novel approaches that can increase the antitumor effect of this treatment without increasing toxicity are being investigated.     

Prognostic factors for hematologic cancers

This article reviews the molecular biology of hematologic cancers and the current understanding of prognostic factors for these cancers. Specific molecular biomarkers that have potential as prognostic factors for various hematologic cancers are discussed. Quantitative and statistical methods of evaluating the usefulness of prognostic factors are presented.     

Solid cancers after bone marrow transplantation.

PURPOSE: To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS: We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS: Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION: The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.     

异基因外周血造血干细胞移植联合骨髓移植治疗白血病30例

 目的　观察异基因外周血干细胞移植联合骨髓移植对白血病的疗效。方法　白血病患者30例,平均年龄32.6岁,其中急性髓细胞白血病（AML） 11例,急性淋巴细胞白血病（ALL） 14例,慢性粒细胞白血病（CML）5例,供者均为HLA相合同胞,动员方案为每天G-CSF 5 μg／kg,共5 d,并于外周血干细胞回输当天采集供者骨髓300 ml回输;预处理方案采用Bu／Cy,移植物抗宿主病（GVHD）预防采用环孢素A（CsA）联合甲氨蝶呤（MTX）、吗替麦考酚酯（MMF）。结果　回输外周血单个核细胞（5.13±2.6）×108／kg,骨髓单个核细胞（1.3±0.6）×108／kg,30例患者均成功植活,其中中性粒细胞＞0.5×109／L的时间为（12.1±3.25）d,血小板＞0.5×109／L的时间为（14.0±5.33）d;Ⅰ～Ⅱ度aGVHD发生率为40.0 %（12／30）,Ⅲ～Ⅳ度发生率3.3 %（1／30）,cGVHD发生率为43.3 %（13／30）,严重cGVHD发生率为3.3 %（1／30）;2年无病生存率达72.0 %。结论　异基因外周血造血干细胞移植联合骨髓移植是治疗白血病的有效方法,并有可能减少重度急、慢性GVHD的发生。     

Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.     

Bone marrow transplantation for hematologic malignancies in patients aged 30 years or older

During the past 10 years, 86 patients 30 to 54 years of age with hematologic malignancies were prepared with high-dose radiochemotherapy and received histocompatible bone marrow grafts. Thirty-four of these patients are surviving for 4 months to 9 years (median, 26 months) following marrow transplantation and 32 of them are in continuing complete remission (CR). Disease-free survival is 44% for 37 patients who were in first remission of acute leukemia or in the chronic phase of chronic granulocytic leukemia (CGL), 23% for 39 patients whose leukemia had relapsed at least once before transplantation or who had advanced stages of CGL, and 60% for ten patients who had hematologic malignancies other than leukemia. The median age of the surviving 34 patients is 36 years (range, 30 to 43 years). The incidence of moderate to severe acute graft-v-host disease (GVHD) was 48% and of chronic GVHD, 26%. The major causes of failure were interstitial pneumonia in 31 patients (24 of whom had antecedent acute GVHD) and recurrent leukemia in 12 patients (11 of whom had either never entered a CR or had relapsed at least once with acute leukemia or had progressive CGL before transplantation). Our data warrant further prospective studies in patients with hematologic malignancies who are older than 30 years.     

Arsenicals in hematologic cancers

Arsenic trioxide (AT) has been the object of renewed interest as a therapeutic since studies in China in the late 1980s confirmed its efficacy in the treatment of acute promyelocytic leukemia (APL). These studies have been replicated in the West, with complete remissions achieved in 80% to 90% of patients with refractory or relapsed APL. The drug has been relatively well tolerated. The dose used for treatment of APL (0.15 mg/kg/d) is approximately 50% of the maximum-tolerated dose (MTD). Common side effects have included fatigue, rash, fluid retention, and QTc-interval prolongation on electrocardiogram. A "retinoic acid syndrome," similar in its manifestations to that noted after administration of all-trans retinoic acid (RA), has been observed in APL patients. Recent studies have included dose-ranging trials to determine pharmacokinetics and the optimum schedule of administration, and studies of possible mechanisms of action. Promising future trials include combining AT with RA in the treatment of newly diagnosed APL, and broadening the range of AT therapy to other leukemias, lymphomas, multiple myeloma and some solid tumors.     

Digestive complaints in patients with hematologic malignancies undergoing bone marrow transplantation

The aim of this study was to assess the severity and frequency of complaints affecting the digestive system in 57 patients with hematological malignancies, who underwent allogeneic (Group I, n = 22) and autologous (Group II, n = 35) hematopoietic stem cell transplantation. Chemotherapy-related toxicities affecting the digestive system (mucositis, nausea/vomiting, diarrhea) were assessed according to the WHO scale for organ toxicity. Selection of the feeding route (oral or parenteral) depended on the tolerance to oral nutrition. Parenteral nutrition (PN) was introduced when oral intake represented ≤ 50% of the total energy requirement over 2 days. PN was started in the third 24-h period. 63.6% of patients undergoing allogeneic transplantation and 54.3% of patients undergoing autologous transplantation needed PN. Ailments affecting the digestive system began in both groups during the administration of conditioning chemotherapy and gradually decreased in the posttransplantation period. Mucositis grade 3/4 requiring PN was observed in 85% patients in Group I and 52.7% patients in Group II. In Group I, grade 3 diarrhea was observed only in patients requiring PN. Severe grade 3/4 organ toxicity from chemotherapy was the main indication for PN in patients undergoing hematopoietic stem cell transplantation.     

Bone marrow transplantation as potential therapeutic strategy to cancers

During a period from 1973 to September, 1981 allogeneic(Allo-) and syngeneic (Syn-) marrow transplantation (BMT) was performed in Japan according to Thomas' method to 41 patients with acute leukemia, 6 of whom (15%) have survived in long-term (3 1/2 years at maximum). This result was roughly compared with that obtained by Thomas et al. until 1977. Interstitial pneu-monia and infections were the main (80%) cause of death. Since October, 1980, following Thomas, recommendation, our BMT team performed Allo-BMT to 5 leukemic patients in complete remission, 2 of whom (40%) are for 14 and 10 months post-transplant in unmaintained remission. According to the previously described method, our BMT team performed autologous BMT (Auto-BMT) to 4 patients with acute leukemia and 11 with several cancers of undifferentiated cell type. The 4 leukemics achieved earlier complete remission, but all died of relapse, thus suggesting that Auto-BMT is only one of supportive therapies. Results of Auto-BMT performed to 5 patients with malignant lymphoma, encouraged by our experience of Allo-BMT to a patient with malignant lymphoma of CS IV, who survived with no chemotherapy 10 1/2 months posttransplant, showed that one patient is alive for 22 months posttransplant in unmaintained remission, and patients have relapsed 2, 6 and 14 1/2 months posttransplant, but are still alive for 25, 14 and 28 months posttransplant, respectively, well responding to chemotherapy. One of 2 patients with nasopharyngeal carcinoma is healthy for 2 years posttransplant in unmaintained remission. The remaining 5 patients died of either infections or relapse. Relapse in both Allo- and Auto-BMT cases, and infectious complications, and no covering of expenses for BMT by health insurance were main problems in Japan and how to solve them were discussed. As compared to Allo-BMT, Auto-BMT seems to be a safe and convenient strategy against solid tumors.     

Bone marrow transplantation for acute lymphoblastic leukemia(all)

Advances in the treatment of childhood acute lymphoblastic leukemia (ALL) have been striking while results have been less impressive in adults who develop this disease. Obvious differences in a patient’s ability to withstand cytotoxic therapy may account, in part, for these findings, but the biologic behaviour of the disease in the two age groups appears to be different; relapses are more frequent and cures less common in adults. In fact, age alone appears to be the most important prognostic factor in ALL. The demonstration of the efficacy of bone marrow transplantation in advanced disease as well as the marked improvements in supportive care and the development of effective high-dose cytotoxic preparative regimens, especially those which use total body irradiation, however, have paved the way for transplantation in first complete remission. Formerly, most adult ALL patients who underwent bone marrow transplant did so in relapse, or in second or subsequent remission. In most studies 40–50 % of first remission adult patients attain long-term disease-free survival after allogeneic and autologous bone marrow transplant. Relapses are considerably higher in the autologous transplant group when compared to the allogeneic group, but the latter population may experience increased morbidity and mortality due to graft-versus-host disease and opportunistic infection. These differences may reflect the beneficial graft-versus-leukemia effect in the allograft as well as infusion of autoiogous leukemia cells in the autograft but neither transplant subtype appears superior. Compared to more conventional approaches, however, transplantation may offer improved disease-free survival, although patient selection appears to significantly influence outcome. These many inherent biases must be noted when comparing markedly different approaches,e.g. transplantversus conventional therapy. The challenge of demonstrating which therapy is superior for adult ALL patients can only be addressed in a well-designed, prospective, randomized trial.     

Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.     

High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases

BACKGROUND: The progressively increasing number of long-term survivors after allogeneic bone marrow transplantation (allo-BMT) led researchers to focus on the early and late complications of this procedure. Endocrine dysfunction occurred mostly in patients who had undergone total body irradiation (TBI) as part of pretransplantation treatment. The extent to which chemotherapy and immune system derangement affect endocrine function in allo-BMT recipients is still unclear. METHODS: Forty consecutive patients (21 women, 19 men) with hematologic diseases surviving 12 or more months after allo-BMT from HLA-identical siblings were studied. Patients' age at transplantation ranged from 13 to 45 years and their post-BMT follow-up lasted 12-62 months. The conditioning regimen BUCY2 was employed. Graft versus host disease (GVHD) was observed in the acute form in 13 patients and in the chronic form in 26. The function of hypothalamic-pituitary-gonad, thyroid, somatotrophic, and adrenal axes was assessed. RESULTS: The most common endocrine dysfunction was ovarian insufficiency (95% of women), followed by an increase in follicle-stimulating hormone in 47% of men, indicating spermatogenesis damage. Hormone replacement therapy was contraindicated in three women because of chronic liver GVHD and it was ineffective partially in four others because of reduced intestinal or cutaneous absorption. Thyroid dysfunction occurred in 47.5% of patients and included low T3 syndrome, chronic thyroiditis, and transient subclinical hyperthyroidism and subclinical hypothyroidism. Adrenal function was abnormal in 10%, mostly related to the prolonged corticosteroid treatment. IGF-I was lower than age-reference values in 27% of all patients and in 38% of those with chronic GVHD. Thyroid, adrenal, and IGF-I impairments were more frequent in patients with chronic GVHD than in patients without this disease (P = 0.048). CONCLUSIONS: A high prevalence of endocrine dysfunction was detected in a cohort of allo-BMT recipients not treated by TBI. Although gonadal failure was likely related to intensive myeloablative treatments, thyroid, adrenal, and IGF-I impairments were late events, suggesting that immunosuppressive treatment and immune system derangement may play a role in the development of endocrine dysfunction after allografting.     

High-dose cyclophosphamide, thio-TEPA, etoposide with autologous bone marrow transplantation for refractory cancers

We studied high-dose chemotherapy with autologous bone marrow transplantation (ABMT) for 10 patients with malignant lymphoma or breast cancer refractory to conventional chemotherapy. Conditioning regimen was consisted of cyclophosphamide 60 mg/kg/day, thio-TEPA 6 mg/kg/day, Etoposide 500 or 600 mg/m2/day for 3 consecutive days. Of 9 patients with measurable lesions, there were 5 with complete responses (CR) and 4 with partial responses (PR). Severe bone marrow suppression, mucositis, and diarrhea were observed in all patients. Furthermore, biliary stasis, which was unpredictable side effect, was observed in most patients. So, mucositis and/or hepatotoxicity were thought to be the dose-limiting factors. But these were not life-threatening and clinically manageable. All patients were received recombinant human granulocyte colony stimulating factor (rhG-CSF) at a dose of 300 micrograms/m2/day and which was effective for shortening the duration of leukopenia. In vitro Colony Forming Unit-granulocyte macrophage assay (CFU-GM assay) showed a significant correlation between the ability of colony formation and the days to recovery of granulocytes.     

Intensive cytoreductive therapy followed by autologous bone marrow transplantation for patients with hematologic malignancies or solid tumors

Fifty patients were studied. Twenty patients with non-Hodgkin's lymphomas (NHL) of high-grade malignancy and 21 patients with acute leukemia (AL) were treated with high-dose cyclophosphamide and total body irradiation, and three patients with Hodgkin's disease (HD) and six patients with solid tumors were treated with high-dose cyclophosphamide and VP16-213. Those procedures were followed by autologous bone marrow transplantation (ABMT). All patients had received conventional chemo(radio)therapy before the ABMT procedure. Although remissions were obtained in patients with cytotoxic drug-resistant diseases (lymphomas and solid tumors), none has become a long-term survivor, as occurred also in patients with solid tumors in partial remission (PR). Two of five patients with NHL in PR at the time of ABMT have become long-term disease-free survivors (28+, 56+ months). Ten patients with NHL were treated in complete remission (CR) and seven are in unmaintained CR; four with long follow-up (14+ to 59+ months). All patients with AL were treated in CR; two patients received ABMT in second CR, and both relapsed. Ten of nineteen patients in first CR relapsed; eight are alive in CR, five with long follow-up. Four deaths were therapy-related, all were patients in poor clinical condition. Intensive cytoreductive therapy followed by ABMT can produce prolonged disease-free survival (and probably cure) in a fair number of patients with poor risk NHL in CR and PR and probably also in patients with acute myeloblastic leukemia in first CR. This procedure was not successful in achieving long-term disease-free survival in patients with refractory lymphomas or solid tumors.     

Allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials

Peripheral blood stem cells have emerged as an alternative to bone marrow for allogeneic transplantation. To elucidate the advantages and disadvantages of research evidence related to the effects of allogeneic peripheral blood stem cells transplantation (PBSCT) and bone marrow transplantation (BMT) for hematological malignancies, we conducted a systematic review of the literature of randomized controlled trials comparing PBSCT to BMT. We systematically searched Cochrane Library, MEDLINE, EMBASE and CNKI up to May 2011. Two reviewers independently identified the eligible studies and assessed the methodological quality of included trials. The relevant data were extracted and analysed using RevMan 5.1. Ten trials totaling 1224 patients have been assessed. Pooled comparisons of studies of PBSCT and BMT found that the overall survival in PBSCT group was non-significantly different from that in BMT group [RR 0.92, 95% CI (0.80-1.07)]. The disease-free survival and relapse rate in PBSCT group were significantly different from that in BMT group [RR 0.67, 95% CI (0.52-0.86) and RR 0.51, 95% CI (0.34-0.76), respectively]. The number of days to reach the absolute neutrophil and platelet count were shorter with PBSCT. The rates of acute and chronic graft-versus-host disease (GVHD) in PBSCT group were significantly higher than that in the BMT group. The mortality in PBSCT group was non-significantly different from that in BMT group. We concluded that PBSCT was associated with a similar overall survival and mortality, improved disease-free survival and a decrease in relapse, faster engraftment, more GVHD when compared with BMT in transplantation for hematologic malignancies.     

Recovery after stem-cell transplantation for hematologic diseases.

PURPOSE: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION: These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.     

Non-myeloablative hematopoietic cell transplantation as immunotherapy for hematologic malignancies

Conventional approaches to hematopoietic stem cell transplantation (HSCT) carry risks of morbidity and mortality from regimen-related toxicities, which have restricted the procedure to relatively young patients in good medical condition. This age restriction is unfortunate because the median age of patients with most candidate diseases (e.g., acute and chronic leukemias, myelodysplasia, myeloproliferative diseases, myeloma, and non-Hodgkin lymphoma) for HSCT is greater than 60 years. In non-myeloablative allogeneic HSCT, high-dose cytotoxic therapy as the conceptual basis for treating hematopoietic malignancies has been replaced by graft-versus-tumor effects. The use of potent pre- and postgrafting immunosuppression derived from preclinical studies has allowed omission of myeloablative cytotoxic therapy without compromising hematopoietic donor cell engraftment. This results in a marked reduction in transplant-related toxicities which makes older or medically infirm patients candidates for this treatment option. Initial results in patients with a variety of hematologic malignancies have been encouraging, with documented sustained cytogenetic and molecular remissions in a substantial number of sometimes heavily pretreated and previously refractory patients. While patients with hematologic malignancies will likely require conversion to full donor hematopoiesis for long-term disease control, a state of mixed donor/host hematopoietic chimerism might suffice to 'cure' the disease phenotypes in various non-malignant diseases. Strategies aimed at inducing donor-specific tolerance and optimizing post-transplant immunosuppression may eventually eliminate the need for pre-transplant total body irradiation which is relevant for minimizing late toxicities.     

Rauscher leukemia as a model for studies of marrow transplantation therapy: results using syngeneic, allogeneic and hybrid donors.

SJL/J mice with leukemia induced in their own cells by Rauscher leukemia virus were treated by marrow transplantation therapy. The results obtained using syngeneic, hybrid and two different allogeneic donors were compared. All types of donor tissue produced some degree of protection; the lowest was yielded by SJL/J cells and the highest by C57BL/10J. The incidence of leukemia recurrence after therapy varied with the donor strain used. The highest and earliest recurrence was seen with SJL/J donors. The use of leukemia-resistant SJB10F₁ hybrids resulted in protracted remissions followed by late relapse, which was possibly related to reemergence of host leukemogenic clones not previously eliminated by the pretransplant marrow ablation treatment. A distinctly different pattern of late deaths was seen with the use of allogeneic donors, suggesting a possible graft-vs-leukemia effect. Graft-vs-host (GvH) response was not evident following transplantation of either the hybrid or syngeneic marrow, as determined from studies using normal SJL/J mice as recipients. GvH disease was found using both types of allogeneic donors, C57BL/10J and 129/J. However, although both allogeneic donors were of the same histocompatibility type, H-2^b, they differed in the level of fatal GvH response induced when used as donors. This suggests the possibility of an influence of « minor » histocompatibility factors affecting GvH response incidence and animal survival. The similarities between the model and the results of treatment of human leukemia by marrow transplantation therapy are discussed, and the possible future use of the model to study means of achieving lower leukemia recurrence through better marrow ablation, and to study the question of whether there is a graft-vs-leukemia effect related to GvH response, is proposed.     

Effect of continuous intravenous administration of high-dose G-CSF on hematologic recovery following autologous purged bone marrow transplantation

Delay in peripheral blood recovery is a common complication of autologous purged bone marrow transplantation. To overcome this problem, we examined the effect of continuous intravenous administration of high-dose G-CSF on hematologic recovery following autologous bone marrow transplantation (auto-BMT) with purged bone marrow. Continuous intravenous administration of high dose G-CSF significantly facilitated the recovery of platelet counts and reticulocyte counts compared to one-hour bolus intravenous injection of the usual-dose G-CSF, although both ways of administration facilitated the recovery of leukocyte counts. The results showed continuous intravenous administration of high-dose G-CSF was useful to facilitate the recovery of not only leukocytes but also reticulocytes and platelets following auto-BMT with purged bone marrow in certain situations. Continuous i.v. administration of high-dose G-CSF may be one of the safest and most useful modes facilitating the hematopoietic recovery following auto-BMT with purged bone marrow.