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Biomedical subjects

Brenda M Sandmaier

Publications and source records attributed to Brenda M Sandmaier.

At least 37 records · Page 2Linked to original sources
PubMed2005

HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia.

We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m2 and 2 Gy of total body irradiation as treatment for patients with chronic myeloid leukemia who were ineligible for conventional HCT. Data from 21 consecutive patients in first chronic phase (CP1; n = 12), accelerated phase (AP; n = 5), second CP (CP2; n = 3), and blast crisis (n = 1) were analyzed. Stem cell sources were bone marrow (n = 4) or granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs; n = 17). The patient who underwent transplantation in blast crisis died on day 21 (too early to be evaluated for engraftment) from progressive disease. Sustained engraftment was achieved in 5 of 12 patients who underwent transplantation in CP1, 4 of 5 patients who underwent transplantation in AP, and 2 of 3 patients who underwent transplantation in CP2, whereas 9 patients rejected their grafts between 28 and 400 days after HCT. Specifically, 1 of 4 marrow recipients and 10 of 17 G-PBMC recipients achieved sustained engraftment. Graft rejections were nonfatal in all cases and were followed by autologous reconstitution with persistence or recurrence of chronic myeloid leukemia. Seven of 11 patients with sustained engraftment--including all 5 patients in CP1, 2 of 4 patients in AP, and neither of the 2 patients in CP2--were alive in complete cytogenetic remissions 118 to 1205 days (median, 867 days) after HCT. Two of the remaining 4 patients died of nonrelapse causes in complete (n = 1) or major (n = 1) cytogenetic remissions, and 2 died of progressive disease. Further efforts are directed at reducing the risk of graft rejection by exclusive use of G-PBMC and increasing the degree of pretransplantation immunosuppression.

Adult↗
PubMed2005

Comparison of lung function after myeloablative and 2 Gy of total body irradiation-based regimens for hematopoietic stem cell transplantation.

Lung function decline is a well-recognized occurrence after myeloablative hematopoietic stem cell transplantation (HCT) that has not been studied after nonmyeloablative conditioning regimens. We examined the lung function of patients before and after 2-Gy total body irradiation-based nonmyeloablative and myeloablative preparative regimens. Before HCT, at day 100, and 1 year after HCT, nonmyeloablative patients had lower 1-second forced expiratory volume (FEV1), forced vital capacity, total lung capacity, residual volume, and carbon monoxide diffusion capacity. However, after transplantation, the risk for experiencing a >20% per year decrease of FEV 1 was significantly lower for nonmyeloablative than myeloablative patients >50 years of age (odds ratio, 0.3; 95% confidence interval, 0.1-0.8; P = .01). Lower pretransplantation FEV 1 was associated with a higher mortality rate for both groups, with the highest mortality risk among patients with a pretransplantation FEV 1 <60% (nonmyeloablative: hazard ratio, 3.9; 95% confidence interval, 1.9-8.0; myeloablative: hazard ratio, 7.2; 95% confidence interval, 2.5-21.2). These results suggest that despite having worse lung function, patients who receive the 2-Gy total body irradiation-based nonmyeloablative regimen will likely experience less pulmonary toxicity than patients who receive a myeloablative regimen, and this may have important clinical implications when deciding on a conditioning regimen for patients >50 years of age with compromised pretransplantation lung function.

Adult↗
PubMed2005

Comparison of ARF after myeloablative and nonmyeloablative hematopoietic cell transplantation.

BACKGROUND: Acute renal failure (ARF) occurs with significant frequency after myeloablative and nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Myeloablative (conventional) HCT is the standard of care for cure of various malignant disorders. The newer modality of nonmyeloablative ("mini-allo") HCT is reserved for patients with advanced age and comorbidities who are ineligible for myeloablative HCT. The present study compares the incidence of ARF between patients undergoing concurrent myeloablative and nonmyeloablative HCT in the same period at the same institution. METHODS: This retrospective cohort study from 1997 to 2003 compares 140 myeloablative and 129 nonmyeloablative patients from the Fred Hutchinson Cancer Research Center. Severity of ARF was classified into 4 grades based on the increase in serum creatinine levels in the first 100 days after HCT. Mortality was studied at 100 days and 1 year. RESULTS: Nonmyeloablative patients were significantly older and had greater pretransplantation comorbidity at baseline. Despite this, patients undergoing myeloablative HCT had a greater incidence of severe ARF (grades 2 and 3, 73% versus 47%; P < 0.001). The incidence of dialysis also was 4-fold greater (12% versus 3%; P < 0.001) in the myeloablative than nonmyeloablative group. On multivariate analysis after controlling for baseline characteristics, myeloablative HCT was associated with a 4.8-fold greater incidence of ARF compared with nonmyeloablative HCT. Nonrelapse mortality also was greater in the myeloablative group at 100 days and 1 year. CONCLUSION: The incidence and severity of ARF, as well as nonrelapse mortality, occurring after nonmyeloablative HCT is significantly lower compared with myeloablative HCT.

Acute Kidney Injury↗
PubMed2005

Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning.

PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient immunosuppression for allogeneic engraftment. However, it was observed that allogeneic immunocompetent cells transplanted with the stem cells, or arising from them, mediated therapeutic antitumor effects independent of the action of the high-dose therapy. This was termed a graft-versus-tumor effect. This has prompted the recent development of nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation that have opened the way to include elderly patients and those with comorbid conditions. RECENT FINDINGS: Recent retrospective studies comparing hematopoietic stem cell transplantation after myeloablative or nonmyeloablative regimens suggested that the use of nonmyeloablative conditioning might be associated with lower transplant-related toxicity, lower nonrelapse mortality, and at least similar intermediate-term progression-free survival. SUMMARY: Hematopoietic stem cell transplantation after nonmyeloablative conditioning might become the procedure of choice also for younger patients. Phase 3 studies are needed to determine outcomes for different diseases and age groups.

Animals↗
PubMed2005

Prognostic relevance of 'early-onset' graft-versus-host disease following non-myeloablative haematopoietic cell transplantation.

We retrospectively analysed outcomes among 395 patients with haematologic malignancies who underwent non-myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched related (n = 297) or unrelated donors (n = 98) in order to identify a possible correlation between the time of onset of graft-versus-host disease (GVHD) and survival. The non-myeloablative regimen consisted of 2 Gy total body irradiation with or without fludarabine, followed by postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. The cumulative incidences of grades II-IV acute GVHD and extensive chronic GVHD were 45% and 47%, respectively, with related donors, and 68% and 68%, respectively, with unrelated donors. High-dose corticosteroid treatment for acute or chronic GVHD was started at a median of 79 (range, 8-799) days and 30 (range, 5-333) days after transplantation from related and unrelated donors respectively. With related donors, the cumulative incidence of non-relapse mortality among patients with GVHD was 55% at 4 years when prednisone was started before day 50 (n = 72), compared with 29% when treatment was started after day 50 (n = 115) (P < 0.001). With unrelated donors, time to onset of treatment for GVHD was not associated with survival. Patients with early-onset GVHD after non-myeloablative HCT from HLA-identical related donors might benefit from intensified primary immunosuppressive treatment.

Acute Disease↗
PubMed2005

Targeted cancer therapy using radiolabeled monoclonal antibodies.

Radioimmunotherapy (RIT) combines the advantages of targeted radiation therapy and specific immunotherapy using monoclonal antibodies. RIT can be used either to target tumor cells or to specifically suppress immunocompetent host cells in the setting of allogeneic transplantation. The choice of radionuclide used for RIT depends on its distinct radiation characteristics and the type of malignancy or cells targeted. Beta-emitters with their lower energy and longer path length are more suitable to target bulky, solid tumors whereas alpha-emitters with their high linear energy transfer and short path length are better suited to target hematopoietic cells (normal or malignant). Different approaches of RIT such as the use of stable radioimmunoconjugates or of pretargeting strategies are available. Encouraging results have been obtained with RIT in patients with hematologic malignancies. The results in solid tumors are somewhat less favorable but new strategies for patients with minimal residual disease using adjuvant and locoregional treatment are evolving. This report outlines basic principles of RIT, gives an overview of available radionuclides and radioimmunoconjugates, and discusses clinical results with special emphasis on their use in hematologic malignancies including use in conditioning regimens for bone marrow transplantation.

Animals↗
PubMed2004

Allogeneic hematopoietic cell transplantation for metastatic renal cell carcinoma after nonmyeloablative conditioning: toxicity, clinical response, and immunological response to minor histocompatibility antigens.

PURPOSE: This phase I trial assessed the safety, efficacy, and immunologic responses to minor histocompatibility antigens following nonmyeloablative allogeneic hematopoietic cell transplantation as treatment for metastatic renal cell carcinoma. EXPERIMENTAL DESIGN: Eight patients received conditioning with fludarabine and low-dose total body irradiation followed by hematopoietic cell transplantation from an HLA-matched sibling donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for donor engraftment of myeloid and lymphoid cells, for clinical response by serial imaging, and for immunologic response by in vitro isolation of donor-derived CD8(+) CTLs recognizing recipient minor histocompatibility (H) antigens. RESULTS: All patients achieved initial mixed hematopoietic chimerism with two patients rejecting their graft and recovering host hematopoiesis. Four patients developed acute, grade 2 to 3, graft-versus-host disease and four patients developed extensive chronic graft-versus-host disease. Five patients had progressive disease, two patients had stable disease, and one patient experienced a partial response after receiving donor lymphocyte infusions and IFN-alpha. CD8(+) CTL clones recognizing minor H antigens were isolated from five patients studied. Clones from three patients with a partial response or stable disease recognized antigens expressed on renal cell carcinoma tumor cells. CONCLUSIONS: Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. CD8(+) CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft-versus-tumor effect. Such antigens may represent therapeutic targets for posttransplant vaccination or adoptive T-cell therapy to augment the antitumor effects of allogeneic hematopoietic cell transplantation.

Adenocarcinoma, Clear Cell↗
PubMed2004

Radioimmunotherapy with bismuth-213 as conditioning for nonmyeloablative allogeneic hematopoietic cell transplantation in dogs: a dose deescalation study.

BACKGROUND: Using a canine model of nonmyeloablative hematopoietic cell transplantation (HCT), the authors demonstrated that pretransplant radioimmunotherapy with the alpha-emitter bismuth-213 (Bi) coupled to anti-CD45 or anti-T-cell receptor alphabeta (TCRalphabeta) monoclonal antibodies (mAb), together with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine A (CsA), achieved stable engraftment of dog leukocyte antigen (DLA)-identical marrow. Engraftment was achieved with doses of 3.6 to 8.8 mCi/kg Bi, but signs of liver toxicity were noted in all dogs. To find a safe and effective dose for further trials, the authors performed a dose deescalation study in 15 dogs with 2.7 to 0.8 mCi/kg Bi. METHODS: Bi was linked to the mAb using the metal-binding chelate CHX-A"-DTPA. All dogs received three to six injections of Bi linked to anti-CD45 or anti-TCRalphabeta mAb followed by marrow grafts from DLA-identical littermates and postgrafting MMF and CsA. RESULTS: During follow-up of greater than 30 weeks, engraftment remained stable in all evaluable dogs conditioned with 1.4 to 2.1 mCi/kg Bi-anti-CD45 or 2.0 to 2.7 mCi/kg Bi-anti-TCRalphabeta. Only one dog conditioned with 1.5 mCi/kg Bi-anti-TCRalphabeta had stable engraftment, whereas two rejected their grafts. In both groups, all dogs conditioned with less than 1.3 mCi/kg Bi rejected their grafts. No signs of graft-versus-host disease or other toxicities were noted. Only mild and transient elevation of liver function tests occurred in 4 of 15 dogs. CONCLUSIONS: This study demonstrates that dose deescalation of radioimmunotherapy with Bi labeled to anti-CD45 or anti-TCRalphabeta as conditioning for nonmyeloablative HCT minimizes toxicity without compromising engraftment. With a dose of 2 mCi/kg Bi, further trials using radioimmunotherapy with Bi for nonmyeloablative HCT seem feasible.

Animals↗
PubMed2004

Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma.

We carried out HLA-matched related (n = 16) and unrelated (n = 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n = 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses.

Adult↗
PubMed2004

Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

We analyzed the kinetics of donor engraftment among various peripheral blood cell subpopulations and their relationship to outcomes among 120 patients with hematologic malignancies given hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning consisting of 2 Gy total body irradiation (TBI) with or without added fludarabine. While patients rapidly developed high degrees of donor engraftment, most remained mixed donor/host chimeras for up to 180 days after HCT. Patients given preceding chemotherapies and those given granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts had the highest degrees of donor chimerism. Low donor T-cell (P = .003) and natural killer (NK) cell (P = .004) chimerism levels on day 14 were associated with increased probabilities of graft rejection. High T-cell chimerism on day 28 was associated with an increased probability of acute graft-versus-host disease (GVHD) (P = .02). Of 93 patients with measurable malignant disease at transplantation, 41 achieved complete remissions a median of 199 days after HCT; 19 of the 41 were mixed T-cell chimeras when complete remissions were achieved. Earlier establishment of donor NK-cell chimerism was associated with improved progression-free survival (P = .02). Measuring the levels of peripheral blood cell subset donor chimerisms provided useful information on HCT outcomes and might allow early therapeutic interventions to prevent graft rejection or disease progression.

Adolescent↗
PubMed2004

Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors.

Nonmyeloablative regimens for allogeneic hematopoietic cell transplantation (HCT) have been developed for patients ineligible for myeloablative conditioning. We compared regimen-related toxicities (RRTs) and nonrelapse mortality (NRM) in 73 nonmyeloablative and 73 myeloablative recipients of HLA-matched related donor HCT, using the National Cancer Institute (NCI) Common Toxicity Criteria. Nonmyeloablative regimens were 2 Gy total body irradiation (TBI), either alone (n = 40) or combined with fludarabine, 30 mg/m(2)/d for 3 days (n = 33). Posttransplantation immunosuppression included mycophenolate mofetil and cyclosporine. Myeloablative regimens consisted mostly of cyclophosphamide + TBI or busulfan + cyclophosphamide, followed by posttransplantation methotrexate and cyclosporine. Nonmyeloablative patients were at higher risk than ablative patients because of greater age, longer time from diagnosis to HCT, more frequent preceding high-dose HCT, and higher pretransplantation Charlson comorbidity scores. Nevertheless, they experienced significantly less severe toxicities in 7 organs/systems: hematologic, gastrointestinal, hepatic, hemorrhage, infection, metabolic, and pulmonary. This translated into less NRM at day 100 (3% versus 23%, P = 10(-4)) and 1 year (16% versus 30%, P =.04). In multivariate analysis, the strongest factor predicting lessened RRT and NRM was nonmyeloablative conditioning, whereas high pretransplantation comorbidity scores predicted higher NRM. In conclusion, nonmyeloablative regimens had lower RRT and NRM and could be considered for comparative studies, including younger patients with more favorable Charlson comorbidity scores.

Adult↗
PubMed2004

Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities.

We have carried out HLA-matched unrelated donor hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in patients with hematologic malignancies who were ineligible for conventional transplantations because of age, comorbidities, or both. The nonmyeloablative regimen consisted of 90 mg/m2 fludarabine and 2 Gy total body irradiation given before and mycophenolate mofetil and cyclosporine given after HCT. This report compares, retrospectively, morbidity and mortality among 60 consecutive patients given nonmyeloablative conditioning (nonablative patients) to those among 74 concurrent and consecutive patients given myeloablative conditioning (ablative patients) before unrelated HCT. The Charlson Comorbidity Index was used to assess pretransplantation comorbidities. Even though nonablative patients had significantly higher pretransplantation comorbidity scores, were older, and had more often failed preceding ablative transplantations and cytotoxic therapies, they experienced fewer grades III to IV toxicities than ablative patients. Further, the incidence of grades III to IV acute graft-versus-host disease (GVHD) was significantly lower in nonablative patients. Both patient groups had comparable 1-year probabilities of chronic GVHD. The 1-year nonrelapse mortality rate was 20% in nonablative patients compared to 32% in ablative patients (hazard ratio=1.4). After adjustment for pretransplantation differences between the 2 patient groups, the hazard ratio was 3.0 (P=.04). Multivariate analyses showed higher pretransplantation comorbidity scores to result in increased toxicity and mortality.

Adolescent↗
PubMed2004

Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center.

Hematopoietic stem cell transplantation (HCT) in patients with prior or active invasive aspergillosis (IA) is a frequent consideration. We reviewed outcomes of 2319 patients who underwent transplantation between 1992 and 2001 in our institution, among whom 45 patients (1.9%) had a known history of IA before HCT. Posttransplantation IA occurred in 13 of these 45 patients with a pretransplantation history (29%). Nine infections were considered recurrent by anatomic site and timing. Compared with all other patients who received allogeneic HCT during the same period, patients with histories of IA had lower overall survival (56% versus 77%; P =.0001) and higher transplant-related mortality (TRM; 38% versus 21%; P =.0001) 100 days after HCT, associated mainly with IA and other pulmonary complications. Among patients with prior IA, posttransplantation IA occurred more frequently in patients who received <1 month of antifungal therapy before HCT (4/6 versus 6/39; P =.001). The probability of posttransplantation IA and overall survival among patients who received >1 month of antifungal therapy and had resolution of radiographic abnormalities were not different from those of patients without prior IA. Patients with prior IA who received conditioning with total body irradiation (TBI) had higher TRM compared with those who received nonmyeloablative and non-total body irradiation-based regimens (16/31 versus 2/14; P =.024). Thus, the duration of antifungal therapy before transplantation, the resolution of radiographic abnormalities, and conditioning regimens are important variables to consider for minimizing the risk for IA recurrence and TRM after allogeneic HCT.

Academic Medical Centers↗
PubMed2004

Targeted cancer therapy and immunosuppression using radiolabeled monoclonal antibodies.

Radioimmunotherapy (RIT) as a means to target radiation therapy to tumor cells or to specifically suppress host immunity specifically in the setting of allogeneic transplantation is a promising new strategy in the armory of today's oncologist. Different approaches of RIT such as injection of a stable radioimmunoconjugate or the use of pretargeting are available. The choice of the radionuclide used for RIT depends on its radiation characteristics with respect to the malignancy or cells targeted. beta-Emitters with their lower energy and longer path length are more suitable for targeting bulky, solid tumors, whereas alpha-emitters with their high linear energy transfer and short path length are better suited to target cells or tumors of the hematologic system. Encouraging results have been obtained using these approaches treating patients with hematologic malignancies. While the results in solid tumors are somewhat less favorable, new strategies for patients with minimal residual disease (MRD), using adjuvant and locoregional treatment, are currently being investigated. In this report, we outline basic principles of RIT, give an overview of available radioimmunoconjugates and their clinical applications with special emphasis on their use in hematologic malignancies, including use in conditioning regimens for stem cell transplantation (SCT).

Antibodies, Monoclonal↗
PubMed2004

Acute renal failure after nonmyeloablative hematopoietic cell transplantation.

Acute renal failure (ARF) is a common life-threatening complication after myeloablative allogeneic hematopoietic cell transplantation (HCT). Nonmyeloablative HCT aims to eradicate the malignancy with graft-versus-tumor effect, rather than with high doses of chemoradiotherapy. It may be anticipated that a lower risk of ARF exists in nonmyeloablative HCT as a result of the milder preconditioning regimen. However, the patients who receive the nonmyeloablative HCT are older individuals who are not eligible for the more toxic allogeneic myeloablative procedure. The goal of this study was to evaluate ARF in a large group of patients who received nonmyeloablative HCT. This cohort study enrolled patients who were undergoing nonmyeloablative HCT at four major centers from 1998 to 2001. Conditioning therapy involved total body irradiation 2 Gy +/- fludarabine 30 mg/m2. Posttransplantation immunosuppression consisted of cyclosporine or tacrolimus and mycophenolate mofetil. ARF was classified into four grades, similar to previous studies in the literature. Collectively, 253 patients were recruited into this study. ARF (>50% decrease in GFR) occurred in 40.4% of patients over a 3-mo period, with 4.4% of patients requiring dialysis. The overall mortality in the study population was 34% at 1 yr. The mortality increased with worsening grade of ARF. The combined need for dialysis and artificial ventilation was associated with a mortality exceeding 80%. Although the number of patients who develop ARF is significant, the risk of developing ARF that requires dialysis after nonmyeloablative HCT is infrequent despite the older age of the patients. The data are also suggestive that ARF may contribute to mortality after nonmyeloablative HCT.

Acute Kidney Injury↗
PubMed2004

Vaccination with Theratope (STn-KLH) as treatment for breast cancer.

Cancer vaccines have demonstrated that they can stimulate antibody and cell-mediated immune responses against tumor-associated antigens in the laboratory. However, few clinical studies with cancer vaccines have demonstrated convincing clinical responses. Sialyl-Tn is a carbohydrate associated with MUC1. It is a unique tumor-associated antigen, present on many adenocarcinomas including breast, ovarian, colorectal, gastric and pancreatic. Consequently, Sialyl-TN is an ideal candidate for boosting the patient's immune system specifically against a unique tumor-associated antigen. The cancer vaccine Theratope was developed by Biomira, Inc. using a synthetic Sialyl-Tn antigen that emulates the unique carbohydrate on human cancer. Clinical trials have predominantly been carried out in breast cancer patients and these trials are outlined in this profile.

Animals↗
PubMed2003

Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning.

This study retrospectively analyzed data from 446 patients given hematopoietic cell transplants from HLA-matched related or unrelated donors after conditioning with 2 Gy total body irradiation with or without fludarabine and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine following grafting. Fifty-three of 446 patients received donor lymphocyte infusion (DLI) with a median CD3 dose of 1 x 10(7) cells/kg. Their diagnoses included myelodysplastic syndrome (n = 10), acute leukemia (n = 10), chronic leukemia (n = 11), multiple myeloma (n = 9), lymphoma (n = 9), and solid tumors (n = 4). Patients received DLI for persistent disease (n = 8), disease relapse (n = 17), progressive disease (n = 12), low donor chimerism with disease (n = 11), or low chimerism with disease remission (n = 5). Seventeen of the 53 patients (32%) are alive with a median follow-up of 30 months; 5 are in complete remission (CR), 2 are in partial remission (PR), and 10 have stable or progressive disease. Nine of 53 patients (17%) developed grades II to IV acute graft-versus-host disease. Of 48 patients receiving DLI for treatment of disease, 7 achieved CR and 5 PR, with an overall response rate of 25%. Six of 16 patients who received DLI for chimerism had increases in donor chimerism leading to sustained engraftment, whereas 10 eventually rejected their grafts. In conclusion, DLI is a potential treatment strategy, with acceptable toxicity, for patients with persistent, relapsed, or progressive disease after nonmyeloablative hematopoietic cell transplantation.

Adolescent↗