Search PubMed⌕ Search

Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 73 records · Page 4Linked to original sources
PubMed1996

Close simulation of acute graft-versus-host disease by interleukin-2 administered after autologous bone marrow transplantation for hematologic malignancy.

The high relapse rate of hematologic malignancy treated with autologous bone marrow transplantation (ABMT) may reflect the absence of a graft-versus-leukemia (GVL) effect usually associated with graft-versus-host disease (GVHD). The purpose of this study was to determine whether administration of interleukin-2 (IL-2) early after ABMT might induce or exacerbate acute skin GVHD. Fourteen patients at high risk for post-transplant relapse, eight with NHL and six with AML > or = first relapse, were conditioned with chemotherapy and total body irradiation (13) or chemotherapy alone (1), and received purged (10) or unpurged (4) marrow. A median of 35 days (range 25-58) after ABMT, they received a 5-day induction course of Roche IL-2 (9 x 10(6) U/m2/day) followed by apheresis, reinfusion of LAK cells, and a 10-day maintenance course of IL-2 (0.9 x 10(6) U/m2/day), all by continuous i.v. infusion. Serial skin biopsies were obtained before and after IL-2 therapy and were read blindly. Patients were studied prospectively for the development of acute cutaneous GVHD as reflected by rash ( > or = 25% body surface area), skin biopsy ( > or = grade II histologic changes) and T cell infiltration as assessed by staining of the biopsy with antibodies UCHL-1 and TIA-1. No patient had a rash before IL-2 therapy, but 12 of 14 (85%) developed a rash during the IL-2 induction course. Before IL-2 therapy, biopsies from three of 10 patients (30%) revealed histologic GVHD; after induction IL-2, biopsies from 11 of 14 patients (79%) revealed grade II acute GVHD. Biopsies from all patients with histologic GVHD after IL-2 therapy contained TIA-1 positive T cells. HLA-DR was negative in the keratinocytes of these paraffin-embedded sections. One patient died early of sepsis, one patient required and responded to topical corticosteroids and 12 had spontaneous resolution of the rash. Six patients relapsed at 3-13 months, while seven remain in complete remission 32+ to 41+ months after ABMT. The results demonstrate that IL-2 therapy after ABMT can induce effects which histologically and clinically mimic cutaneous acute GVHD in most patients. Prospective, randomized trials of IL-2 vs observation after transplantation of autologous marrow or stem cells for high-risk NHL and AML have been initiated which may allow us to determine whether this phenomenon is associated with a clinical GVL effect as reflected by a decreased relapse rate.

Acute Disease↗
PubMed1996

Long-term cryopreservation of bone marrow for autologous transplantation.

Little is known about the effect of long-term cryopreservation on the viability of hematopoietic stem cells (HSC) or on the success of autologous bone marrow transplantation. Although progenitor cell assays such as culture of CFU-GM after thawing can be predictive of engraftment, the most rigorous assay for the cryosurvival of HSC is engraftment after reinfusion of stem cells. We retrospectively evaluated the engraftment data for 36 patients with hematologic malignancies or solid tumors treated at the Fred Hutchinson Cancer Research Center between 1981 and 1993 who received bone marrows stored for 2 years or more. The median duration of cryopreservation for this study group was 2.7 years (range 2.0-7.8). Ninety-seven percent of patients in the study group achieved a granulocyte count of > or = 0.5 x 1.0(9)/1 at a median of 19 days (range 10-115) vs 86% of control group (selected by diagnosis and date of storage) at a median of 20 days (P = 0.14). Seventy percent of patients in the study group achieved a platelet count > or = 20 x 10(9)/1 at a median of 27 days (range 9-69) vs 74% of control group at a median of 23 days (P = 0.47). Also, samples of 28 marrows cryopreserved for a median of 4.4 years (range 2.0-7.8) were cultured to determine if a loss of hematopoietic progenitors relative to duration of storage could be detected. The storage length was not predictive for the quantity of colonies formed (P = 0.57 for BFU-E-derived colonies; P = 0.65 for CFU-GM-derived colonies). We found no consistent detrimental effect of long-term cryopreservation on the success rate of autologous bone marrow transplantation. This report confirms previous reports that marrow cells cryopreserved for several years are capable of engrafting. Therefore, bone marrow cells may be stored at an early appropriate time before the side-effects of multiple cycles of chemotherapy and radiotherapy on hematopoietic tissues are incurred.

Adolescent↗
PubMed1996

Busulfan, cyclophosphamide and fractionated total body irradiation for autologous or syngeneic marrow transplantation for acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels.

In a previous phase I study, it was concluded that tolerable doses of busulfan (BU), cyclophosphamide (CY) and total body irradiation (TBI) were 8 mg/kg, 60 mg/kg and 12.0 Gy, respectively, for autologous marrow transplant recipients. In an attempt to decrease the variability of BU steady-state concentration (Css) following oral dosing, a BU dose escalation study based on targeted plasma levels was performed in patients receiving autologous transplants for AML or syngeneic transplants for CML. In this study, the BU dose was adjusted up or down based on observed plasma concentration. All patients received a fixed dose of CY 60 mg/kg and TBI of 12 Gy. The first dose level evaluated was 8.6 mg/kg with a target BU Css of 511 ng/ml. Eight patients were entered at this level and the median BU Css achieved was 441 (range 253-566). One of eight patients developed grade 3-4 regimen-related toxicities (RRT). The oral dose of BU for dose level II was 10.6 mg/kg with a target Css of 632 ng/ml. Six patients were entered at this level and median BU Css achieved was 642 (range 566-674). One of six patients developed grade 3-4 RRT. The oral dose for dose level III was 12.6 mg/kg with a target BU Css of 754 ng/ml. Five patients with AML were entered at this dose level and the median plasma BU Css was 733 ng/ml (682-900). Two of five (40%) patients at dose level III developed grade 3-4 RRT which was considered excessive making dose level II the MTD. This study showed that targeted BU Css can reliably be achieved with a bias of -5.23% and mean absolute error of 11.3%. Overall, targeting made a -32.5% to 158.3% change in plasma BU Css as compared to expected BU Css based on first dose pharmacokinetics if targeting were not performed in this study. Thus, targeting avoided much of the variability in BU Css seen in other studies and appears to have allowed for an increase in oral dosing from 8 mg/kg to 10.6 mg/kg. Despite achieving higher and more uniform BU Css, there was no apparent effect on relapse or survival, although the number of patients evaluated was small.

Acute Disease↗
PubMed1996

Microbial contamination of peripheral blood stem cell collections.

We prospectively evaluated microbiologic cultures for a series of 1263 peripheral blood stem cell harvests collected from 376 sequential patients. The incidence of microbial contamination was 0.23% of all samples, or 47% of samples from patients not receiving systemic antibiotics. This incidence of positive microbial cultures is less than that for cultures of bone marrow (3.8%) after harvesting and before further processing. Of the three positive cultures, two grew coagulase-negative Staphylococcus and the third, Streptococcus viridans. Two patients were reinfused with cultured-positive PBSC components, and neither exhibited the same organism in subsequent blood cultures. Although microbial contamination may occur during peripheral blood stem cell collection and cryopreservation, this report indicates that PBSC contamination does not play a conspicuous role in the infectious complications of PBSC transplantation.

Bacteriological Techniques↗
PubMed1996

High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer.

This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell transplantation for metastatic breast cancer. Twenty-two patients with stage IV breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had primary refractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone only disease, six had bone plus visceral disease, and eight had loco-regional recurrent disease. The median time for diagnosis to transplant was 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not evaluable (NE) for response because of NED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-transplant. The patient who was NED at time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieved a complete response (CR) (44%), five achieved a partial response (PR) (31%) and five had no response (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in refractory relapse, and both patients treated in responding relapse achieved a CR. Of the seven patients who achieved CR, three are alive and disease-free on days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post-transplant. One patient in CR died of aspergillus pneumonia on day 306 post-transplant. The median day to progression in five patients who achieved a PR after transplantation was 335 (range 144-507). The probabilities of survival and event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22 patients. The probability of EFS at 2 years for the eight patients achieving CR (including one patient who was NED at transplant) was 0.33. The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest that high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstrating that BU is an active agent in this disease and could be incorporated into treatment regimens requiring hematopoietic stem cell support.

Adult↗
PubMed1996

Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma.

This study was performed to determine the factors influencing the collection of autologous peripheral blood stem cells (PBSC) in patients with multiple myeloma (MM) who had disease which had progressed after an initial response or who had refractory disease. Fifty-seven patients with MM underwent PBSC collections following recombinant human granulocyte colony stimulating factor (G-CSF) alone (n = 19) (16 micrograms/kg/day), cyclophosphamide (CY) (4 gm/m2 x 1) with either G-CSF (10 micrograms/kg/day) (n = 7) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (500 micrograms/m2/day) (n = 7) or cyclophosphamide (4 gm/m2 x 1) and etoposide (200 mg/m2/day x 3) (CE) with G-CSF (10 micrograms/kg/day) (n = 24). The goal was to collect 5 x 10(6) CD34+ cells/kg. Fifty of 57 patients underwent autologous transplantation with PBSC alone (n = 39) or PBSC + marrow (n = 11). The median yield of CD34+ cells was 7 x 10(6)/kg (range 0-178.3). Thirty-nine of 57 patients (68%) achieved the target level of 5 x 10(6) CD34+ cells/kg in a median of three (range 1-8) collections. Eighteen (32%) patients yielded < 5 x 10(6) CD34+ cells/kg with the first collections. Thirteen of these 18 patients yielded < 2.5 x 10(6) and five yielded 2.5-4.95 x 10(6) CD34+ cells/kg. Of the 18 patients with less than optimal CD34+ cell yields, five with CD34+ yields of 2.5-4.95 x 10(6)/kg received PBSC alone at transplant, six underwent marrow storage to augment the PBSC dose and received PBSC plus marrow and seven patients underwent secondary collections. Of seven patients who underwent second (n = 5) or third (n = 2) cycles of PBSC collections using G-CSF 16 (n = 4) or 32 (n = 3) micrograms/kg/day, > 2.5 x 10(6) CD34+ cells/kg were collected in four patients. Two patients achieved < 0.18 CD34+ cells following three cycles of mobilization. In a linear regression model, an increased percentage of marrow involvement and prior radiotherapy (RT) were statistically significantly associated with a low CD34+ cell collection yield (P = 0.003, and 0.01, respectively). A mobilization regimen of CE plus G-CSF was associated with a significantly higher yield of CD34+ cells as compared to patients receiving G-CSF alone (P = 0.02). CY with G or GM-CSF was not significantly different than G-CSF alone (P = 0.49). Twenty-two of 24 (92%) patients receiving CE with G-CSF achieved a target level of 5 x 10(6) CD34+ cells/kg or more as compared to 11 of 19 (58%) patients receiving G-CSF alone (P = 0.01) and six of 14 (43%) patients receiving CY with G or GM-CSF (P = 0.001). These data suggest that percentage of marrow involvement, prior radiotherapy, and number of prior chemotherapy regimens are important predictors of PBSC yield in patients with MM. These data also suggest that CE plus G-CSF is superior to G-CSF alone or CY plus G/GM-CSF based on mean daily CD34+ cell collection yield. Higher doses of G-CSF (16-32 micrograms/kg/day) can result in adequate CD34+ cell collections in some secondary attempts in patients with MM failing an initial mobilization regimen.

Adult↗
PubMed1996

Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease.

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.

Adolescent↗
PubMed1996

Autologous transplantation with peripheral blood stem cells collected after granulocyte colony-stimulating factor in patients with acute myelogenous leukemia.

The use of peripheral blood stem cells (PBSC) with or without bone marrow (BM) in patients with acute myelogenous leukemia (AML) undergoing autologous transplantation in untreated first relapse (Rel1) or in second remission (CR2) was evaluated in a phase II study. Twenty-three patients with AML in untreated Rel1 (n = 8) and CR2 (n = 15) underwent autologous transplant using PBSC with (n = 19) or without (n = 4) BM. Six patients received busulfan (BU) and cyclophosphamide (CY) and 17 received BU, CY and total body irradiation prior to transplant. The median number of CD34+ cells infused was 4.81 x 10(6)/kg (range 0.04-15). Fifteen of 23 patients received post-transplant interleukin-2 (IL-2) at a median of 43 days (range 11-93) in an attempt to decrease relapses. The median day of recovery of granulocytes to 0.5 x 10(9)/I was 12 (range 8-27) and platelets to 20 x 10(9)/I was 15 (range 8-103). Patients received a median of 4 units (range 0-20) of red blood cells and 29 units (range 4-252) of platelets. The probability of 100 day non-relapse mortality was 0.14. The probabilities of survival and relapse at 2 years were 0.24 and 0.65, respectively. The probabilities of relapse in patients receiving (n = 15) and not receiving (n = 8) interleukin-2 (IL-2) were 0.59 and 0.74, respectively (P = 0.1). Overall, seven of 23 (30%) patients are alive and continuously disease-free at a median of 483 days (range 113-835) post-transplant. These data demonstrate that the infusion of PBSC collected after rhG-CSF corrected engraftment problems previously observed with autologous BM transplants in patients with AML but was associated with a high relapse rate.

Acute Disease↗
PubMed1996

High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells.

Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.

Adolescent↗
PubMed1996

Syngeneic marrow transplantation in patients with multiple myeloma.

Eleven patients with advanced multiple myeloma (MM) received syngeneic marrow (n = 10) or peripheral blood stem cell (n = 1) transplants following cyclophosphamide (CY) and total body irradiation (TBI) (n = 8), busulfan (Bu) and CY (n = 1), Bu, CY and TBI (n = 1) or Bu, melphalan and thiotepa (n = 1). At the time of transplant one patient had stage II and 10 patients had stage III disease. Four patients had refractory disease, two had chemotherapy sensitive disease and five had progressed after an initial response to chemotherapy. The median time from diagnosis to transplant was 353 days (range 176-6118). After transplant, the median time to achieve granulocytes of 0.5 x 10(9)/l and platelets of 20 x 10(9)/l was 12 days (range 9-20) and 12 days (9-27), respectively. One patient died of interstitial pneumonia syndrome on day 32 and one died of veno-occlusive disease of the liver on day 44 post-transplant, and these were unevaluable for response. Five of nine evaluable patients achieved a complete response (CR), three a partial response, and one patient had no response. Three patients who did not achieve CR died of progressive disease 106, 142 and 321 days post-transplant. Of five patients who achieved a CR, three relapsed on days 539, 737 and 1706 and died on days 1759, 1596 and 1736, respectively; one patient died of myelodysplastic syndrome on day 1407 without evidence of MM and one patient is alive and disease-free 3297 days after transplant. One of the two long-term survivors has a persistent monoclonal protein in the blood 15 years post-transplant. These data show that high-dose therapy and infusion of normal syngeneic marrow cells can cure a small fraction of patients with MM. However, the majority of patients did not achieve durable CR, demonstrating the need for improved transplant conditioning regimens, earlier transplant or additional post-transplant treatment strategies when syngeneic transplants are performed.

Adult↗
PubMed1996

Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia.

The association of mixed (donor/host) chimerism with graft-versus-host disease (GVHD), graft rejection, disease recurrence and survival was investigated in 116 patients with aplastic anemia and 197 patients with chronic myelogenous leukemia (CML) transplanted with unmodified marrow from an HLA-identical sibling donor of opposite sex. Patients with aplastic anemia were conditioned with cyclophosphamide (CY), patients with CML were conditioned with a combination of CY and total body irradiation (TBI) or busulfan. Sixty-three of the patients with aplastic anemia (54%) and 100 patients with CML (51%) were categorized as mixed chimeras based on the concurrent presence of donor and host lymphohematopoietic cells 14 days or later after transplantation. The TBI dose used for conditioning was inversely correlated with the development of mixed chimerism (P < 0.0001) among CML patients. No other patient- or transplant-related parameter was identified which contributed significantly to the development of mixed chimerism. The incidence of rejection was higher but not significantly so in patients with aplastic anemia who were mixed chimeras. The incidence of leukemic relapse in patients with CML who were mixed chimeras was increased only if mixed chimerism occurred after day 100 (P = 0.015). The incidence of acute GVHD (grades II-IV) was lower in mixed chimeras than in complete chimeras, but this difference was statistically significant only for patients with aplastic anemia given single-agent GVHD prophylaxis (P = 0.0008). Mixed chimeras in that group also had a better survival than complete chimeras, while no significant difference was observed in patients with aplastic anemia given drug combinations for GVHD prophylaxis. Among patients with CML, both overall survival (P = 0.03) and relapse-free survival (P = 0.04) were significantly superior in mixed than in complete chimeras. Thus, mixed chimerism was frequent among patients with aplastic anemia and with CML and was not uniformly associated with graft failure or leukemic relapse. The interaction between conditioning regimen, GVHD prophylaxis and chimerism are complex. The survival advantage of mixed chimeras is only in part related to a lower incidence of GVHD and other factors are likely to contribute.

Adolescent↗
PubMed1996

A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery.

To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.

Adolescent↗
PubMed1995

Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment.

A retrospective study compared posttransplant engraftment parameters in 203 patients with myelofibrosis (MF) with those in a population of 203 matched controls without MF. There were no significant differences between these groups in the proportions of patients who died without achieving engraftment and in the disease-free survival distributions. Furthermore, comparisons between the two groups of patients reaching the respective endpoints showed no differences in the time distributions for reaching 0.5 or 1.0 x 10(9)/L granulocytes, but the time to platelet transfusion independence was 3 days longer in patients with MF. In further analysis, results for 33 patients with severe MF were compared with those of their respective controls. The proportions of patients with severe MF who died without reaching these engraftment endpoints and the disease-free survival distributions in the two groups were similar. Among patients who reached the respective engraftment endpoints, there was no statistically significant difference in the pace of granulocyte recovery. In patients with severe MF, there was a 7-day delay in the time to reach platelet transfusion independence and a 2-day delay in the time to reach red blood cell independence, but the differences were not statistically significant. The present results do not substantiate concerns raised by earlier studies. MF may delay the time to reach platelet independence by approximately 3 days and may increase platelet transfusion requirements, but no other perturbation of hematopoietic reconstitution was apparent.

Adolescent↗
PubMed1995

Unrelated donor marrow transplantation in children.

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.

Adolescent↗
PubMed1995

A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia.

The present study was performed as a retrospective analysis of the role of pretransplant splenectomy to determine the incidence of late bacterial infections, acute and chronic graft-versus-host disease (GVHD), relapse, and survival among 358 patients receiving HLA-identical marrow grafts for chronic myelogenous leukemia. Sixty-eight (19%) of the 358 patients had undergone splenectomy before transplantation. There was a trend towards more grade II-IV acute GVHD among splenectomized patients, but this was not significant in the multivariate analysis. The incidence of chronic GVHD was similar for splenectomized and nonsplenectomized patients. Late infectious complications did not significantly differ between splenectomized and control patients (rates per patient year were 0.16 and 0.14, respectively). The overall risk of leukemic relapse was significantly increased for splenectomized patients (56% v 32% for controls, P = .001) and control patients with splenomegaly (P < .0001). Splenectomy and splenomegaly remained significant and independent hazards for relapse in the multivariate analysis (hazard ratio [HR], 1.82, P = .029; and HR, 1.49, P = .002; respectively). Relapse was also increased in patients with advanced disease (HR, 2.95; P = .0001), in patients with T-cell-depleted marrow (HR, 4.51; P = .0001), and in the female donor and male recipient combination (HR, 1.74; P = .044). Patients with splenectomy had an increased overall mortality (HR, 1.18), but this was not statistically significant in the multivariate analysis. In summary, our study showed no significant influence of splenectomy on late posttransplant infections, acute or chronic GVHD, or overall survival. There was no evidence that splenectomy decreased recurrence of chronic myelogenous leukemia.

Abscess↗