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Biomedical subjects

M J Zhang

Publications and source records attributed to M J Zhang.

At least 19 recordsLinked to original sources
PubMed2001

Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.

Adolescent↗
PubMed2001

Role of PTCH and p53 genes in early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common skin cancer in the Western world. Ultraviolet (UV) exposure, race, age, gender, and decreased DNA repair capacity are known risk factors for the development of BCC. Of these, UVB irradiation from sunlight is the most significant risk factor. The incidence of sporadic BCC increases in individuals older than age 55, with the greatest incidence reported in individuals who are older than 70, and is rare in individuals who are younger than 30. In this study, we analyzed 24 BCC samples from individuals who had BCC diagnosed by the age of 30. Fifteen single-stranded conformation polymorphism variants in the PTCH gene were identified in 13 BCC samples. Sequence analysis of these single-stranded conformation polymorphism variants revealed 13 single nucleotide changes, one AT insertion, and one 15-bp deletion. Most of these nucleotide changes (nine of 15) were predicted to result in truncated PTCH proteins. Fifteen p53 mutations were also found in 11 of the 24 BCC samples. Thirty-three percent (five of 15) and 60% (nine of 15) of the nucleotide changes in the PTCH and p53 genes, respectively, were UV-specific C-->T and CC-->TT nucleotide changes. Our data demonstrate that the p53 and PTCH genes are both implicated in the development of early-onset BCC. The identification of UV-specific nucleotide changes in both tumor suppressor genes suggests that UV exposure is an important risk factor in early onset of BCC.

Adolescent↗
PubMed2001

The effect of graft purging with 4-hydroperoxycyclophosphamide in autologous bone marrow transplantation for acute myelogenous leukemia.

BACKGROUND: Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia cells (4HC purging). No large controlled trials evaluating efficacy and toxicity of 4HC purging are reported. METHODS: We studied 294 patients reported to the Autologous Blood and Marrow Registry receiving either a 4HC-purged (n = 211) or unpurged (n = 83) autograft for AML in first (n = 209) or second (n = 85) remission. Analyses were restricted to patients transplanted less than 6 months after achieving remission. Using Cox proportional hazards regression, we compared time to treatment failure (death or relapse, inverse of leukemia-free survival) after 4HC-purged vs unpurged transplants while controlling for important prognostic factors. RESULTS: Median duration of posttransplant neutropenia was 40 (range, 10-200) days after 4HC-purged transplants and 29 (9-97) days after unpurged transplants (p < 0.01). Transplant-related mortality was similar in the two groups. In multivariate analysis, patients receiving 4HC-purged transplants had lower risks of treatment failure than those receiving unpurged transplants (relative risk, 0.69, p = 0.12 in the first posttransplant year; relative risk, 0.28, p < 0.0001 thereafter). Adjusted three-year probabilities of leukemia-free survival (95% confidence interval) were 56% (47-64%) and 31% (18-45%) after 4HC-purged and unpurged transplants in first remission, respectively. Corresponding probabilities in second remission were 39% (25-53%) and 10% (1-29%). CONCLUSION: Grafts purged with 4HC are associated with higher leukemia-free survival after autologous bone marrow transplants for AML.

Acute Disease↗
PubMed2001

Confidence bands for the difference of two survival curves under proportional hazards model.

A common approach to testing for differences between the survival rates of two therapies is to use a proportional hazards regression model which allows for an adjustment of the two survival functions for any imbalance in prognostic factors in the comparison. When the relative risk of one treatment to the other is not constant over time the question of which therapy has a survival advantage is difficult to determine from the Cox model. An alternative approach to this problem is to plot the difference between the two predicted survival functions with a confidence band that provides information about when these two treatments differ. Such a band will depend on the covariate values of a given patient. In this paper we show how to construct a confidence band for the difference of two survival functions based on the proportional hazards model. A simulation approach is used to generate the bands. This approach is used to compare the survival probabilities of chemotherapy and allogeneic bone marrow transplants for chronic leukemia.

Adolescent↗
PubMed2001

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗
PubMed2001

Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis.

In this paper, we describe modern statistical methods for presentation of the results of studies of bone marrow transplantation. We focus here on 'univariate' or unadjusted techniques to describe the outcomes of such studies. In another paper we will discuss multivariate methods. We discuss the type of data one may have available to make inference about outcomes. We explain the differences between the Kaplan-Meier estimator of the survival function and the cumulative incidence curve, how these curves should be interpreted and when each is the appropriate summary statistic. We discuss the weighted log rank statistic and show how different weights can be used to put emphasis on detecting differences between groups in different time periods. We also present a simple estimate of current leukemia-free survival which is useful in summarizing post-transplant events.

Analysis of Variance↗
PubMed2001

Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling.

In this paper, we address methods of multivariate regression. We discuss the value of regression compared to matched pairs analysis, methods of coding variables, basic concepts of the Cox model and interpretation of results of the Cox model. We present methods of handling variables whose effect changes with time. We present methods to check the assumptions of the Cox regression. Finally, and perhaps most importantly, we provide suggestions for presenting the results in clear and thorough tables and graphs.

Bone Marrow Transplantation↗
PubMed2001

PTCH mutations in squamous cell carcinoma of the skin.

Ultraviolet light exposure is the major risk factor for the development of squamous cell carcinoma in Caucasians. Mutations in the tumor suppressor gene p53 have been identified in both squamous cell carcinomas and basal cell carcinomas. The human homolog of the Drosophila patched gene, has been shown to be mutated in sporadic basal cell carcinomas; however, mutations in the patched gene have not been found in squamous cell carcinoma. In this study, we screened a total of 20 squamous cell carcinoma samples for mutations in the patched gene. Using polymerase chain reaction-single strand conformation polymorphism as an initial screening method, we identified one non-sense mutation, two mis-sense mutations and three silent mutations in five squamous cell carcinoma samples. In one squamous cell carcinoma sample, we identified a tandem GG-->AA transitional change at nucleotide 3152 in exon 18 of the patched gene that resulted in a premature stop codon at codon 1051. The three squamous cell carcinoma samples containing non-sense and mis-sense mutations were isolated from individuals with histories of multiple basal cell carcinoma. Sequence analysis of the p53 gene in these five squamous cell carcinoma samples identified one CC-->TT and three C-->T ultraviolet-specific nucleotide changes. Our study provides evidence that the patched gene is mutated in squamous cell carcinoma from individuals with a history of multiple basal cell carcinoma. The identification of ultraviolet-specific nucleotide changes in both tumor suppressor genes supports the notion that ultraviolet exposure plays an important part in the development of squamous cell carcinoma.

Aged↗
PubMed2001

Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: effect of HLA disparity, ABO incompatibility, and method of T-cell depletion.

Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV-positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.

ABO Blood-Group System↗
PubMed2001

Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding.

Myofibroblasts have been thought to participate in subepithelial fibrosis in asthma, but the mechanism of myofibroblast induction has not been fully understood. In this study we investigated injury-related myofibroblast induction in a coculture system of guinea-pig epithelial cells and fibroblasts cocultured in a human amnion chamber. After pseudostratified epithelial cells were mechanically scraped, migrated flat epithelial cells differentiated into cuboidal appearances on Day 4 and then returned to their original shapes on Day 8. During the course of the epithelial redifferentiation, it was found by Northern blot analysis, immunohistochemistry for alpha-smooth muscle actin, and electron microscopic observation that the myofibroblasts were transiently induced on Day 4. The myofibroblast induction was inhibited by the blocking of transforming growth factor (TGF)-beta1 and thrombospondin (TSP)-1, indicating that the activation of TGF-beta1 by TSP-1 would induce myofibroblasts. This finding was also supported by a transient upregulation of TSP immunoreactivity and TSP-1 messenger RNA (mRNA) in fibroblasts. Interestingly, epithelial injury reduced TGF-beta1 immunoreactivity in the amnion membrane but did not affect TGF-beta1 mRNA in epithelial cells and fibroblasts, indicating that TGF-beta1 supplied from the extracellular matrix can participate in myofibroblast induction. Concurrently with myofibroblast induction, procollagen type I and III mRNAs were upregulated in fibroblasts, and obvious collagen deposition was observed ultrastructurally around the myofibroblasts compared with the fibroblasts. These results indicate that induced myofibroblasts can be functionally more active in producing collagen than are resting fibroblasts. The present study suggests that epithelial injury stimulates TGF-beta1 release from the extracellular matrix and its activation via TSP-1 production, causing collagen synthesis through myofibroblast induction.

Actins↗
PubMed2001

[Determination of degraded products of penicillin by high performance liquid chromatography].

A method for the determination of main composition in degraded products of penicillin, 6-aminopenicillanic acid (6-APA), penicillin G kalium (PGK), phenylacetic acid (PAA), and the by-product benzylpenicilloic acid (BPA) by HPLC was studied. Separation conditions were as follows: Spherisorb C18 column, 250 mm x 4.6 mm i.d., 10 micrograms; mobile phase: V (methanol): V(0.004 mol/L KH2PO4 buffer, pH 4.5) = 50:50; flow rate: 1 mL/min; detector: UV 230 nm. The method is effective, quick, accurate and reproducible. The satisfactory results show that this new method has certain practical values as an approach of quality control.

Chromatography, High Pressure Liquid↗
PubMed2000

Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission.

Allogeneic bone marrow transplantation is an effective postremission strategy for patients with acute myelogenous leukemia (AML) in first complete remission (CR). The value of administering consolidation chemotherapy before human leukocyte antigen (HLA)-identical sibling transplantation is not established. Outcomes of patients with AML in first CR receiving no consolidation therapy, standard-dose cytarabine consolidation therapy, and high-dose cytarabine consolidation therapy before HLA-identical sibling transplantation were compared. Five-year treatment-related mortality rates were 30% (95% confidence interval [CI], 18% to 42%) in patients receiving no consolidation chemotherapy, 22% (95% CI, 17% to 28%) in those receiving standard-dose cytarabine consolidation, and 24% (95% CI, 17% to 31%) in those receiving high-dose cytarabine (P = NS). Five-year cumulative incidences of relapse were 19% (10% to 30%), 21% (16% to 27%), and 17% (11% to 24%), respectively (P = NS). Five-year probabilities of leukemia-free survival were 50% (36% to 63%), 56% (49% to 63%), and 59% (50% to 66%), respectively (P = NS). Five-year probabilities of overall survival were 60% (46% to 71%), 56% (49% to 63%), and 60% (51% to 67%), respectively (P = NS). The data indicate that postremission consolidation with cytarabine before allogeneic transplantation for AML in first CR is not associated with improved outcome compared to proceeding directly to transplantation after successful induction. (Blood. 2000;96:1254-1258)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources.

BACKGROUND: Umbilical-cord blood as an alternative to bone marrow for hematopoietic stem-cell transplantation may lower the risk of graft-versus-host disease (GVHD). METHODS: We studied the records of 113 recipients of cord blood from HLA-identical siblings from the period from 1990 through 1997 and compared them with the records of 2052 recipients of bone marrow from HLA-identical siblings during the same period. The study population consisted of children 15 years of age or younger. We compared the rates of GVHD, hematopoietic recovery, and survival using Cox proportional-hazards regression to adjust for potentially confounding factors. RESULTS: Recipients of cord blood were younger than recipients of bone marrow (median age, 5 years vs. 8 years; P<0.001), weighed less (median weight, 17 kg vs. 26 kg; P<0.001), and were less likely to have received methotrexate for prophylaxis against GVHD (28 percent vs. 65 percent, P<0.001). Multivariate analysis demonstrated a lower risk of acute GVHD (relative risk, 0.41; P=0.001) and chronic GVHD (relative risk, 0.35; P=0.02) among recipients of cord-blood transplants. As compared with recovery after bone marrow transplantation, the likelihood of recovery of the neutrophil count and the platelet count was significantly lower in the first month after cord-blood transplantation (relative risk, 0.40 [P<0.001], and relative risk, 0.20 [P<0.001]), respectively. Mortality was similar in the two groups (relative risk of death in the recipients of cord blood, 1.15; P=0.43). CONCLUSIONS: Recipients of cord-blood transplants from HLA-identical siblings have a lower incidence of acute and chronic GVHD than recipients of bone marrow transplants from HLA-identical siblings.

Acute Disease↗
PubMed2000

Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT).

Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations with results of 536 HLA-identical sibling bone marrow transplantations. No transplants were T-cell depleted. Median follow-up was 12 months, and analyses focused on 1-year outcomes. Recipients of blood stem cell transplants had more rapid recovery of neutrophils to at least 0.5 x 10(9)/L (median time to recovery, 14 days, compared with 19 days for marrow transplants; P <.001) and of platelets to at least 20 x 10(9)/L (median time, 18 days, compared with 25 days for marrow transplants; P <.001). There was no significant difference in the incidence of grades II to IV acute graft versus host disease (GVHD). The incidence of chronic GVHD was significantly higher after blood stem cell transplantation (1-year probability [95% confidence interval], 65% [56%-72%] compared with 53% [47%-59%]; P =.02) Relapse incidence in the 2 transplant groups did not differ significantly. Treatment-related mortality rates were lower and leukemia-free survival rates were higher with blood stem cell transplants in patients with advanced leukemia (acute leukemia in second remission or chronic myelogenous leukemia in accelerated phase) but not in early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in chronic phase). The median time from transplantation to hospital discharge was 23 days after blood stem cell transplantation and 28 days after bone marrow transplantation (P =.003). Further study with longer follow-up is necessary to definitively establish the role of blood stem cells for allogeneic transplantation, especially in patients with good-risk disease. (Blood. 2000;95:3702-3709)

Acute Disease↗
PubMed2000

T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities.

T-cell depletion of donor marrow decreases graft-versus-host disease resulting from transplants from unrelated and human leukocyte antigen (HLA)-mismatched related donors. However, there are diverse strategies for T-cell-depleted transplantation, and it is uncertain whether any improve leukemia-free survival (LFS). To compare strategies for T-cell-depleted alternative donor transplants and to compare T-cell depleted with non-T-cell-depleted transplants, we studied 870 patients with leukemia who received T-cell-depleted transplants from unrelated or HLA-mismatched related donors from 1982 to 1994. Outcomes were compared with those of 998 non-T-cell-depleted transplants. We compared LFS using different strategies for T-cell-depleted transplantation considering T-cell depletion technique, intensity of pretransplant conditioning, and posttransplant immune suppression using proportional hazards regression to adjust for other prognostic variables. Five categories of T-cell depletion techniques were considered: narrow-specificity antibodies, broad-specificity antibodies, Campath antibodies, elutriation, and lectins. Strategies resulting in similar LFS were pooled to compare T-cell-depleted with non-T-cell-depleted transplants. Recipients of transplants T-cell depleted by narrow-specificity antibodies had lower treatment failure risk (higher LFS) than recipients of transplants T-cell depleted by other techniques. Compared with non-T-cell-depleted transplants (5-year probability +/- 95% confidence interval [CI] of LFS, 31% +/- 4%), 5-year LFS was 29% +/- 5% (P = NS) after transplants T-cell depleted by narrow-specificity antibodies and 16% +/- 4% (P <.0001) after transplants T-cell depleted by other techniques. After alternative donor transplantation, T-cell depletion of donor marrow by narrow-specificity antibodies resulted in LFS rates that were higher than those for transplants T-cell depleted using other techniques but similar to those for non-T-cell-depleted transplants. (Blood. 2000;95:3996-4003)

Adolescent↗
PubMed2000

Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in non-small cell lung cancer.

Epidemiological studies have demonstrated a strong association between tobacco use and lung cancer; however, the genetic targets of these carcinogens and the role of other environmental agents in this process have yet to be defined. We examined the contribution of alcohol use and cigarette smoking top53 gene mutations in patients with non-small cell lung cancer. Mutations of the p53 gene were detected by sequence analysis in 105 patients with non-small cell lung cancer. Patient characteristics significantly associated with p53 gene mutations were determined using logistic regression. Mutations in the p53 gene were present in 53% of the patients (56 of 105). p53 mutations were more common in patients who used alcohol than in patients who consumed less than one drink per day (72 versus 39%; P = 0.003), and were detected more often smokers than nonsmokers (58% versus 10%, P = 0.02). Mutations in the p53 gene were present more often (P = 0.01) in alcohol drinkers who smoked cigarettes [76% (31 of 41)], than in nondrinkers (<1 drink per day) who smoked cigarettes [42% (20 of 48)] or in nondrinkers who did not smoke [14% (1 of 7)]. In conclusion, alcohol consumption and tobacco use are both associated with p53 mutations in non-small cell lung cancer. The link between exposure to both alcohol and tobacco and p53 mutations raises the possibility that alcohol may enhance the mutagenic effects of cigarette smoke in the lung.

Aged↗
PubMed2000

Effect of nucleated marrow cell dose on relapse and survival in identical twin bone marrow transplants for leukemia.

The impact of cell dose (number of nucleated donor cells per kilogram recipient weight) on transplantation outcome is controversial and may differ for allogeneic and identical twin (syngeneic) bone marrow transplants. We studied the association between cell dose and outcome in 100 unmanipulated identical twin bone marrow transplantations for leukemia, reported to the International Bone Marrow Transplant Registry between 1985 and 1994, using Cox proportional hazards regression for multivariate analyses. Cell doses ranged from 0.3 to 7.4 x 10(8) nucleated cells/kg (median, 3.0 x 10(8)cells/kg). Median follow-up was 75 months. Five-year cumulative incidences of transplant-related mortality with high (more than 3 x 10(8) cells/kg) versus low (less than or equal to 3 x 10(8) cells/kg) cell doses were 2% (95% confidence interval [CI], 0% to 8%) versus 10% (95% CI, 4% to 20%), respectively. Five-year probabilities of leukemia-free survival were 53% (95% CI, 39% to 67%) and 37% (95% CI, 23% to 52%), respectively. In multivariate analysis, among patients surviving in remission at least 9 months after transplantation, those receiving high cell doses were at significantly lower risk for treatment failure (relapse or death) than those receiving low cell doses (RR, 0.27; 95% CI, 0.12 to 0.6; P =.001). Lower treatment failure resulted from fewer relapses in the high cell dose group (RR for relapse, 0.28; 95% CI, 1.2 to 0.66; P =.003). These findings suggest that outcomes after syngeneic bone marrow transplantation could be improved by transplanting more than 3 x 10(8) nucleated cells per kilogram. The benefit of high cell dose on relapse may represent a delayed graft-versus-leukemia effect.

Adolescent↗