auto-SCT Recipients Research Articles

Comparison of autologous and allogeneic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

ABSTRACT Objectives To analyze the outcomes of patients who received autologous stem cell transplantation (auto-SCT), matched sibling donor stem cell transplantation (MSD-SCT) and haploidentical stem cell transplantation (haplo-SCT) and provide the basis for the choice of transplantation method in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Methods We retrospectively investigated the outcomes of 119 adult patients with Ph+ ALL in our center. The overall survival (OS) rate, leukemia-free survival (LFS) rate, cumulative incidence of relapse (CIR) rate, non-relapse mortality (NRM) rate and the impact of achievement of complete molecular response (CMR) within 3 months and sustaining CMR up to transplantation (s3CMR) on transplantation method were explored. Results The estimated OS, LFS, CIR and NRM rates at 3 years were not significantly different among three groups (p = 0.960, 0.917, 0.375 and 0.096, respectively). For the 65 patients who achieved s3CMR, there was no significant difference in OS (84.5% vs 72.5% vs 100%, p = 0.374), LFS (75.2% vs 64.5% vs 83.3%, p = 0.668), CIR (17.2% vs 8.1% vs 16.7%, p = 0.583) and NRM (3.1% vs 23.4% vs 0%, p = 0.055) among auto-SCT group, MSD-SCT group and haplo-SCT group. However, in patients who did not achieve s3CMR, auto-SCT recipients tended to have higher CIR (60% vs 33.2% vs 24.0%, p = 0.013) than the allo-HSCT group. Conclusions Auto-SCT with maintenance therapy after HSCT appears to be an attractive treatment option for patients with Ph+ ALL especially for those whose s3CMR was kept up to transplantation. For non-s3CMR patients, allogeneic transplantation may be more effective from lower relapse.

Comparative Analysis of Immune Reconstitution in HIV-Positive Recipients of Allogeneic and Autologous Stem Cell Transplant on the BMT-CTN-0903/AMC-080 and BMT-CTN-0803/AMC-071 Trials

Introduction We report the results of a phenotypic and functional analysis of immune reconstitution in HIV(+) patients treated with allogeneic hematopoietic stem cell transplant (allo-HSCT), in comparison with HIV(+) autologous transplant (auto-HSCT) recipients, HIV(-) auto-HSCT recipients and healthy controls (HCs). Methods Blood samples were collected at days 56, 180 and 365 post-transplant from HIV(+) allo-ASCT recipients (n=17, BMT-CTN-0903/AMC-080 trial), HIV(+) auto-SCT recipients (n=36, BMT-CTN-0803/AMC-071 trial) and HIV(-) auto-SCT recipients (n=30, NCT00569309/OSU-07044 trial), and at 1 time point from 71 HCs. Five-color flow cytometry was performed on whole blood. Principal component analysis (PCA) examined global differences across 18 immune cell subsets between all subject cohorts. Wilcoxon rank-sum tests compared median absolute and proportionate cell counts. Feature importance score analysis (FIS) identified contributions of 100 immune cell populations to differences between HIV(+) cohorts and HCs. Functional responsiveness of HIV(+) allo-HSCT recipients' T cells to stimulation with CD3- and CD28-directed antibodies, NK cells to stimulation with IL-12+IL-18 and monocytes to stimulation with lipopolysaccharide (LPS) was assessed by mass cytometry on peripheral blood mononuclear cells (n=2) and compared to HCs (n=2). Results PCA showed that immunomes of HIV(+) allo-HSCT recipients and HIV(+) auto-HSCT recipients clustered together at all time points. HIV(-) auto-SCT recipients and HCs clustered together and away from the HIV(+) cohorts. FIS identified 13 cell subsets that defined the difference between HIV(+) allo-HSCT recipients (all visits) and HCs and 11 immune cell subsets that defined the difference between HIV(+) auto-HSCT recipients (all visits) and HCs; in each comparison, activated CD3+/HLA-DR+ T cells had the greatest impact on the difference between composite HIV(+) and HC immunomes. At 1 year, both HIV(+) transplant recipient cohorts had higher absolute numbers of activated T cells, effector T cells and CD8+ T cells than HCs and lower numbers of CD4+ T cells, naive T cells, and activated NK cells compared to HCs (p Conclusion Chronic HIV infection confers pro-inflammatory immune characteristics on phenotypic and functional profiling of the cellular immunome of stem cell transplant recipients, irrespective of allogeneic or autologous stem cell donor source.

Comparable Results of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia in First Complete Molecular Remission: An Analysis By the Acute Leukemia Working Party of the EBMT

▪ BACKGROUNDThe outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) improved markedly with the introduction of tyrosine kinase inhibitors (TKIs), which allow achieving high rate of molecular remissions. However, allogeneic hematopoietic stem cell transplantation (allo-SCT) performed in first complete remission still remains a standard of care. In a recent study we demonstrated significant improvement of results of autologous hematopoietic stem cell transplantation (auto-SCT) in the era of TKIs [Giebel S, et al.; Eur J Cancer 2014;50:411-7]. The goal of the current analysis was to compare results of auto-SCT and allo-SCT for adult patients with Ph+ ALL in first molecular remission. PATIENTS AND METHODS569 adult patients with Ph+ ALL, treated between 2007-2014 with either auto-SCT (n=67), allo-SCT from matched sibling donor (MSD, n=255) or unrelated donor (URD, n=247) were included in the analysis. The median age for respective groups was 46 (20-65) years, 41 (18-65) years and 40 (18-65) years (p=0.002). Conditioning regimen was myeloablative in all cases and based on either total body irradiation (TBI) (64% in auto-SCT, 78% in MSD-SCT, 74% in URD-SCT) or chemotherapy. Based on available data, all auto-SCT recipients and 95% of allo-SCT recipients were treated with TKIs. RESULTSIn a univariate analysis the incidence of relapse at two years was 47% after auto-SCT, 28% after MSD-SCT and 19% after URD-SCT (p=0.0002). Respective rates of non-relapse mortality (NRM) were 2%, 18% and 22% (p=0.001). The probabilities of leukemia-free survival (LFS) were 52%, 55%, and 60% (p=0.69) while overall survival (OS) rates were 70%, 70% and 69% (p=0.58), respectively. The incidence of chronic graft-versus-host disease (GVHD) for recipients of allo-SCT was 43%.In a multivariate model adjusted for other potential risk factors, the risk of relapse was significantly reduced for URD-SCT as compared to auto-SCT (Hazard Ratio = 0.47, p=0.002). The risk of NRM was increased for both MSD-SCT (HR=14.1, p=0.009) and URD-SCT (HR=16.1; p=0.006). Compared to auto-SCT, a chance of LFS was similar for MSD-SCT (HR=1.1, p=0.53) and URD-SCT (HR=1.03, p=0.9). When referred to auto-SCT, there was a tendency to increased risk of the overall mortality after URD-SCT (HR=1.6, p=0.08) and MSD-SCT (HR=1.5, p=0.12). Among other factors, the use of TBI was associated with reduced risk of relapse (HR=0.65, p=0.02), while increased chance of LFS (HR=0.74, p=0.04) and OS (HR=0.67, p=0.01). CONCLUSIONSIn the era of TKIs results of myeloablative auto-SCT, MSD-SCT and URD-SCT for patients with Ph+ ALL in first molecular remission are comparable. In view of these findings auto-SCT appears an attractive treatment option allowing avoidance of chronic GVHD. Further prospective studies are needed to better discriminate patients who benefit from allo-SCT or for whom the use of auto-SCT may be sufficient. Regardless the type of donor, TBI-based regimens should be considered preferable type of conditioning for adult patients with Ph+ ALL. DisclosuresNo relevant conflicts of interest to declare.

Diarrhea in peripheral stem cell transplant recipients: a developing country's experience.

We aimed to determine the frequency and microbiological causes of diarrhea occurring during the first 100 days in allogeneic (allo-) and autologous (auto-) stem cell transplantation (SCT) patients. A total of 452 patients who underwent transplantation due to hematological or solid organ malignancy were included. From the administration of the conditioning regimen up to day 100 post-transplant, diarrhea cases lasting at least three days with a minimum of three episodes per day were evaluated. Cases of diarrhea were observed in 94 patients out of 227 subjects who received allo-SCT and in 107 patients out of 225 who received auto-SCT. The incidence rate of diarrhea in both patients undergoing autologous and allogeneic transplant was 47.5% and 41.4%, respectively. The cause of the diarrhea could be detected in 20.5% of auto-SCT patients and in 30.8% of allo-SCT patients. Parasitic infections were frequently observed in both autologous and allogeneic transplant patients in the first 20 days. In the late period, significantly more patients developed diarrhea in the allo-SCT recipient group than in the auto-SCT recipients due to graft versus host disease (GVHD) and cytomegalovirus (CMV) colitis. This study revealed the causes of diarrhea and the prevalence and factors of parasitic infections in transplant patients in Turkey. All causative factors of diarrhea should be considered in detail, feces analyses should be evaluated for each patient, and endoscopic biopsy samples should be obtained when required in immunosuppressive patients undergoing stem cell transplantation.

Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin lymphoma

Transplant outcomes of autologous or allogeneic stem cell transplantation (SCT) have not been elucidated as a single cohort in non-Hodgkin lymphoma (NHL). We analyzed the outcomes of 270 adult recipients receiving autologous (auto) SCT (n = 198) or allogeneic (allo) SCT (n = 72) for NHL between the years 2000 and 2010. Five-year overall survival rates for B and T cell NHL were 58% and 50%, respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B and T cell lymphoma, respectively). In multivariate analysis, the number of chemotherapy regimens and disease status pre-SCT were independently associated with long-term outcome after SCT (for both auto- and allo-SCT). We conclude that the type of transplantation offered to patients, based on patient selection and disease-related factors, can achieve long-term survival, highlighting the importance of further improvement in disease control and reducing procedure-related mortality. The role of transplantation needs to be reevaluated in the era of targeted therapy.

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) at High Risk of Cns Relapse

Abstract Abstract 4249 BACKGROUND: Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE: We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS: Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg ( 21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS: To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION: These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures: No relevant conflicts of interest to declare.

Safety of Liposomal Cytarabine Prophylaxis in Pediatric Bone Marrow Transplant (BMT) Recipients with Acute Leukemia (AL) and Non Hodgkin Lymphoma (NHL) At High Risk of CNS Relapse

Abstract 4249 BACKGROUND:Liposomal Cytarabine is a derivative of cytarabine designed for intrathecal or intraomaya treatment of leukemia/lymphomatous meningitis (LLM). This formulation allows for sustained release with prolonged therapeutic concentration and drug exposure of 8 to 14 days in children and adults, respectively. Adult trials have shown liposomal cytarabine 50mg to be both safe and effective in the treatment of LLM (Glantz et al, JCO 1999). Bomgaars et al. investigated the use of liposomal cytarabine in children in a phase I dose escalation trial and demonstrated the maximal tolerated dose to be 35mg and that it was safe, well tolerated and effective (Bomgaars et al., JCO 2004). Comparisons of liposomal cytarabine use with conventional methotrexate prophylaxis suggest an improved quality adjusted survival benefit for patients where any possible additional toxicities are out measured by prolonged overall survival (Cole et al, Cancer 2003). However, there remains a paucity of data on the use of liposomal cytarabine prophylaxis to prevent LLM in pediatric patients, particularly in pediatric allogeneic stem cell (AlloSCT) recipients. Review of the literature reveals conflicting data concerning the efficacy of intrathecal chemoprophylaxis in children with leukemia/lymphoma after hematopoietic stem cell transplant. Recent multicenter trials suggest no statistically significant difference in the incidence of isolated or mixed CNS relapses between children receiving standard post-SCT intrathecal prophylaxis versus those that received no prophylaxis (Rubin et al., BMT 2011). This highlights the need to explore alternative chemoprophylaxis strategies in these high risk patients so that significant progress can be achieved. OBJECTIVE:We report on the safety and tolerability of liposomal cytarabine prior to and following allogeneic or autologous stem cell transplant in pediatric BMT recipients with AL and NHL. METHODS:Pediatric stem cell recipients with a history of AL or NHL and high risk of CNS disease received liposomal cytarabine 35mg (<21yr) or 50mg (>21yr) via lumbar puncture or omaya resevoir pre conditioning and approximately every 3months for 1–2yrs post stem cell transplant. No other intrathecal prophylaxis was administered. Patients received dexamethasone (0.15mg/kg/dose BID) concomitantly × 5days. Eight patients received a 9/10 or 10/10 matched unrelated donor transplant, 1 patient received an 8/10 matched unrelated donor. There were 9 matched related donor transplants and 3 autologous transplants. Twelve patients received a TBI (1200 cGy) based myeloablative conditioning regimen. Seven patients received an additional CNS boost of up to 1200 cGy during conditioning. All allogeneic SCT recipients received GVHD prophylaxis as previously described (Oswunko/Cairo, BBMT 2004; Bhatia et al, BBMT 2009) with tacrolimus and MMF. RESULTS:To date there have been 21 patients: (12 ALL, 2 AML, 3 Burkitt, 3 DLBCL and 1 T-LL). At the time of transplant, 7 patients were CR1/PR1, 10 patients CR2 and 4 patients CR3. Among all patients, they have received a total of 46 doses (median=1, range 1–12). Median age: 12yr (range 6–22). Mean follow up: 517 days (median= 294days). Eight of 21 patients had a history of CNS AL/NHL involvement prior to AlloSCT. No patients had evidence of LLM at the time of AlloSCT. Two patients experienced Grade II-III headache. Grade II-III vomiting was also noted in 2 additional patients. Head CT scans that were done at the time of symptom occurrence were negative for any evidence of hydrocephalus, hemorrhage, infarct or inflammation in all patients. Patients were treated with supportive therapy and had complete resolution of symptoms. Seven patients developed relapsed systemic disease, but none relapsed in the CNS. An additional 3 patients are deceased secondary to multi organ failure and 2 patients from overwhelming infection. However, none of the above patients had CNS AL/NHL at time of death. CONCLUSION:These preliminary results suggest that prophylactic liposomal cytarabine is tolerable and effective in pediatric AlloSCT and AutoSCT recipients at risk for CNS relapse. Larger studies are needed in the future to compare this to other CNS prophylaxis regimens post auto or AlloSCT. In addition, trials are in development to investigate the combination of intraomaya Rituximab followed by liposomal Cytarabine in children with recurrent/refractory CNS CD20+ AL/NHL. Disclosures:No relevant conflicts of interest to declare.

Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over

The safety and efficacy of auto-SCT for lymphoma in older patients is not well established, particularly in those ≥70 years old. We performed a retrospective analysis comparing 17 auto-SCT recipients ≥70 years old with 39 recipients aged 65-69 years. Hematopoietic cell transplantation comorbidity index (HCT-CI) scores were similar in both groups. Nonrelapse mortality (NRM) was increased in patients aged 70 years and older (hazard ratio (HR) 6.04, P=0.0029), and OS was decreased (HR 1.98, P=0.082). 1-year NRM was 35% in patients aged ≥70 years vs 8% in those aged 65-69 years (P=0.017). The incidence of in-hospital falls was higher in those aged ≥70 years (29 vs 8%, P=0.047). In a secondary exploratory analysis, we found that the occurrence of in-hospital falls was strongly associated with inferior OS (HR 3.36, P=0.0023) and NRM (HR 4.60, P=0.009) among all patients of aged 65 years and older. We conclude that auto-SCT is feasible in older patients but that mortality rates appear increased in those over age of 70 years. In-hospital falls were correlated with higher mortality, and prevention of falls may improve outcomes. Susceptibility to falls may indicate underlying frailty and should be explored prospectively as a means of selecting older patients for auto-SCT.

Outpatient reduced-intensity allogeneic stem cell transplantation for patients with refractory or relapsed lymphomas compared with autologous stem cell transplantation using a simplified method

The effectiveness of reduced-intensity conditioning allogeneic stem cell transplantation (allo- RIC) compared with high-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) in Hodgkin's disease (HD) and in non-Hodgkin's lymphoma (NHL) patients remains poorly defined. The purpose of the study was to demonstrate the usefulness of auto-SCT or allo-SCT, employing a RIC regimen in refractory or relapsed NHL or HD patients. We analyzed the outcome of 71 patients with advanced disease. Twenty-three NHL and 14 HD patients received an allo-RIC using fludarabine, cyclophosphamide, and low-dose busulfan as the conditioning regimen. Sixteen NHL and 18 HD patients received auto-SCT using cyclophosphamide and etoposide as conditioning regimen. All hematopoietic stem cells products were not cryopreserved and the majority of grafts were done on an outpatient basis, including conditioning and post-stem cell infusion care (auto-SCT, 62% and allo-RIC procedure, 91%). The median OS was 45.5 months for the allo-RIC recipients and 53.3 months for auto-SCT recipients. Acute/chronic GVHD incidence in NHL and HL groups was 38%/31% and 14%/7%, respectively. We found no significant difference in overall survival between allo-RIC group and auto-SCT group for NHL patients (P = 0.43) but better OS was observed for auto-SCT group than for allo-SCT group in HL patients (P < 0.001). The relapse rate was higher in autografted patients, both in NHL and HD. Both auto-SCT and allo-RIC appear to be valid treatments for poor-risk patients with relapsed or refractory lymphoma who could not otherwise be cured with conventional salvage regimens.

A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Interleukin-12 induced cytolytic activity in lymphocytes from recipients of autologous and allogeneic stem cell transplants.

Interleukin-12 (IL-12) has been reported to enhance the cytolytic activity of NK and activated T cells and to induce low levels of lymphokine-activated killer (LAK) activity in normal human lymphocytes. Therapy with IL-12 has induced tumor eradication in murine models. These observations suggest that IL-12 might have a role as treatment for minimal residual disease following transplantation. To determine whether PBL from recipients of autologous (autoSCT) and allogeneic (alloSCT) bone marrow or peripheral blood stem cell transplants respond to IL-12 with generation of LAK activity, PBL were incubated with IL-12 for 5 days, then tested in a 51Cr release assay for lysis of Daudi. PBL from 17 normal 'control' individuals were similarly tested and lysis was observed in only 3/17 (mean 16.9% of the three). By contrast, PBL from 10/12 patients obtained a median of 30 days after autoSCT, exhibited significant IL-12-induced LAK activity (mean lysis, 35.3%, P < 0.005 vs controls). PBL from 18 of 20 patients tested a median of 44 days after alloSCT also exhibited significant LAK activity (mean lysis, 30.0%, P < 0.005 vs controls). In autoSCT recipients, IL-12 and IL-2 at high concentrations (1000 U/ml each) were additive for induction of LAK activity, whereas low, suboptimal concentration of IL-12 (250 U/ml) and IL-2 (1 U/ml) were synergistic in 3/5 experiments. The percentage of PBL expressing IL-12 receptor beta 1 chain (IL-12r beta 1) was higher in stem cell recipients than in normal individuals, P < 0.05. Moreover, a higher percentage of IL-12r beta 1-positive PBL was associated with greater IL-12-induced LAK activity in transplant recipients. These studies demonstrate that PBL obtained early after stem cell transplantation have a higher percentage of cells expressing IL-12r beta 1 and respond to IL-12 with significantly greater LAK cytotoxicity than PBL from normal controls. These results suggest that IL-12 is a potentially attractive candidate for study as consolidative immunotherapy after stem cell transplantation.