Psychosocial Factors in Decision-Making of Patient Eligibility for Allogeneic Bone Marrow Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3324-3324
Author(s):  
Brian J. Bolwell ◽  
Linda McLellan ◽  
Elizabeth Kuczkowski ◽  
Jane Dabney ◽  
Victoria Wentling ◽  
...  
Keyword(s):  
Decision Making ◽  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Solid Organ Transplantation ◽  
Case Vignette ◽  
Solid Organ ◽  
Allogeneic Bone ◽  
Post Transplant ◽  
Allogeneic Bmt ◽  
Case Vignettes

Abstract Oncologists specializing in bone marrow transplants (BMT) make daily decisions about appropriate medical candidates for allogeneic BMT based on clinical criteria. It is not clear how, and if, patient eligibility decisions are made based on psychosocial criteria. Although setting limits of patient eligibility based on psychosocial criteria has been researched in solid organ transplantation, data is sparse in BMT. This report focuses on physician responses to a psychosocial survey. An IRB approved survey was mailed to members of the ASBMT (North America) mailing list. Of 704 members, 663 were deemed viable respondents: excluded were non-physician members and physicians specializing in research or not working with allogeneic BMT patients. These surveys were mailed in April 2004. As of 7/6/04, 253 surveys were returned, representing a 38% response rate. Average age of responders was 47 years. Average number of years experience in BMT was 14, with a range of 2–39 years. 17 case vignettes were presented. These vignettes asked whether or not it was appropriate to proceed with allo BMT (assuming an appropriate donor was available) based on a specific psychosocial problem. In virtually every case vignette, at least 10% of respondents stated they would not proceed with allogeneic BMT based on the issues raised in the vignette. In seven case vignettes, the majority of respondents stated that they would recommend not proceeding with BMT. The general theme/construct of these 7 vignettes appears to be ability to comply with treatment plans. Specifically, the following were case vignettes in which the majority of respondents recommended not to proceed with transplant: no caregiver available to assist with the patient post-transplant (do not proceed = 70%); the patient is actively alcoholic (do not proceed = 62%); the patient is non-compliant (do not proceed = 75%); the patient is currently suicidal (do not proceed = 84%); the patient is currently using addictive illicit drugs (do not proceed = 73%); the patient has mild dementia (do not proceed = 55%); the patient cannot pay for the transplant (do not proceed = 52%). Conversely, the following case vignettes were less worrisome to the survey respondents, and in general represented surmountable psychosocial and/or clinical issues. These vignettes included; a history of prior suicidal attempts although not currently suicidal (proceed with transplant = 86%); controlled schizophrenia (proceed with transplant = 83%); daily marijuana use (proceed with transplant = 82%); smokes tobacco (proceed with transplant = 79%); morbid obesity (proceed with transplant = 71%); major depression (proceed with transplant = 84%). These findings underline the importance of post-transplant longitudinal care in determining the ultimate success of an allogeneic BMT, and underscore their importance in patient eligibility decision-making. These findings also illustrate that psychosocial variables play a significant role in determining patient eligibility for allogeneic BMT and that there is no clear-cut consensus on this topic, highlighting the need for ongoing clinical research.

scholarly journals The importance of MHC class II in allogeneic bone marrow transplantation and chimerism-based solid organ tolerance in a rat model

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233497
Author(s):  
Kai Timrott ◽  
Oliver Beetz ◽  
Felix Oldhafer ◽  
Jürgen Klempnauer ◽  
Florian W. R. Vondran ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Mhc Class Ii ◽  
Rat Model ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Class Ii ◽  
Allogeneic Bone Marrow ◽  
Solid Organ ◽  
Allogeneic Bone

Allogeneic bone marrow transplantation for hepatocellular carcinoma: hepatocyte growth factor suppresses graft-vs.-host disease

2007 ◽  
Vol 293 (6) ◽  
pp. G1114-G1123 ◽  
Author(s):  
Yasuhiko Yoshida ◽  
Tadamichi Hirano ◽  
Gakuhei Son ◽  
Yuji Iimuro ◽  
Takehito Imado ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Gene Transduction ◽  
Allogeneic Bmt ◽  
Graft Vs Host Disease ◽  
Hepatocyte Growth

Allogeneic bone-marrow transplantation (BMT) can induce a powerful graft-vs.-tumor (GVT) effect not only on hematological malignancies but also on solid tumors. However, graft-vs.-host disease (GVHD) is a major complication of allogeneic BMT. We assessed GVT effect on hepatocellular carcinoma (HCC) and the effects of hepatocyte growth factor (HGF) gene transduction on GVHD in HCC transplanted mice. (C57BL/6 × C3H/HeJ)F1(B6C3F1, H-2bxk) mice were used as recipients and C3H/HeJ(H-2k) mice were used as donors. Hepa1-a (a C57L mouse-derived hepatoma cell, H-2b) was subcutaneously injected into the recipient mice. Tumor bearing mice were treated in the following ways: group 1, no treatment; group 2, total body irradiation (TBI); group 3, TBI and BMT; group 4, TBI and BMT with empty vector; group 5, TBI and BMT with HGF gene transduction; group 6, TBI and BMT with administration of FK506, a representative immunosuppressive agent. Acute GVHD was assessed by histological examination of the liver, small intestines, and large intestines. Tumor growth was markedly suppressed in mice that received an allogeneic BMT. Donor-derived CD8+T cells had infiltrated into the tumor, and cytotoxic CD8+T cells against HCC were present. However, among the four groups that received a BMT, this suppressive effect was weaker in group 6 compared with the other three groups ( groups 3, 4, and 5). HGF gene transduction improved GVHD while preserving the GVT effects. Allogeneic BMT markedly suppresses the growth of HCC. Simultaneous HGF gene transfer can suppress GVHD while preserving the GVT effect.

Clinical Significance of FLT3 Internal Tandem Duplication in Patients with Acute Myeloid Leukemia Who Underwent Allogeneic Bone Marrow Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4419-4419
Author(s):  
Je-Jung Lee ◽  
Yu-Ra Lee ◽  
Hee-Nam Kim ◽  
Nan-Young Kim ◽  
Kyeong-Soo Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Melting Curve ◽  
Disease Free Survival ◽  
Melting Curve Analysis ◽  
Allogeneic Bone ◽  
Intermediate Risk ◽  
Free Survival ◽  
Allogeneic Bmt ◽  
Disease Free

Abstract Since the introduction of high-dose cytarabine therapy, there are still controversies for the role of allogeneic or autologous stem cell transplantation (SCT) in acute myeloid leukemia (AML), but the SCT, especially allogeneic, has a benefit in AML patients with intermediate risk. However, it is needed to investigate for a new prognostic factor, in addition to the cytogenetics, to the further stratifying approach. Internal tandem duplications (ITD) within FLT3 are present in 20–30% of patients with AML and have a prognostic implication in the disease. However, there was no report in AML patients who underwent allogeneic bone marrow transplantation (BMT). In this study, we evaluated the prognostic relevance of FLT3/ITD in 42 patients with AML who underwent allogeneic BMT. FLT3/ITD mutations were studied on bone marrow samples at diagnosis using PCR. As a baseline study, we firstly analyzed the incidence of FLT3/ITD in BM samples at diagnosis of 214 patients with AML. Of the patients, FLT3/ITD were found in 68 patients (31.8%). In this study, 64% of the patients who underwent allogeneic BMT were positive for FLT3/ITD mutations. Methologically, FLT3/ITD detections by melting curve analysis showed higher sensitivity (66.7%) than those by gel electrophoresis (61.9%). There were no significant differences in the engraft periods and the incidence of acute and chronic GVHD according to the presence of FLT3/ITD mutations. When we analyze patient’s survival according to the presence or absence of FLT3/ITD, the probability of overall survival (OS) at 3 years in the AML patients with FLT3/ITD tended to be shorter than those lacking FL3/ITD (53.9 ± 9.9% vs. 60.6 ± 14.7%, P=0.46). In addition, the probability of disease free survival (DFS) at 3 years in the AML patients with and without FLT3/ITD was 57.3±10.3% and 85.7±13.2%, respectively (P=0.046). Among the cytogenetic risk group, low-risk and high-risk groups were no significant differences according to FLT3/ITD despite of the limited number of patients studied. However, patients with intermediate-risk were significantly shorter DFS in the presence of FLT3/ITD than those in the absence of FLT3/ITD (P=0.048). These findings suggest that the presence of FLT3/ITD mutations is a poor prognostic factor for disease free survival in AML patients, especially with cytogenetically intermediate-risk, who underwent allogeneic BMT and melting curve analysis to detect the presence of FLT3/ITD mutations is a useful tool with high sensitivity.

Dynamic Changes and Impact of Myeloid Derived Suppressor Cells in Allogeneic Bone Marrow Transplantation in Mice.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2999-2999
Author(s):  
Dapeng Wang ◽  
Yu Yu ◽  
Kenrick M Semple ◽  
Kelley M.K. Haarberg ◽  
Jianing Fu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Myeloid Derived Suppressor Cells ◽  
Dynamic Changes ◽  
Tumor Relapse ◽  
Allogeneic Bmt

Abstract Abstract 2999 Myeloid-derived suppressor cells (MDSCs) are a group of myeloid cells comprised of hematopoietic progenitor cells and immature macrophages, dendritic cells and granulocytes. MDSCs accumulate in inflammatory diseases and various cancers. In this study, we investigated the dynamic changes and effects of MDSCs in graft-versus-host disease (GVHD) development and/or tumor relapse after allogeneic bone marrow transplantation (BMT). Using murine models of syngeneic and allogeneic BMT, we found that MDSCs transiently accumulated in the blood and spleen of recipients, but returned to the physiological levels shortly after BMT without GVHD. On the contrary, the levels of blood MDSCs always elevated after BMT with GVHD in the recipients of allogeneic BM+T cells. The MDSC accumulation was positively related with the severity of GVHD. In addition, MDSC accumulation was further increased upon tumor relapse. Although MDSCs isolated from both syngeneic and allogeneic BMT recipients inhibited T-cell proliferation under allogeneic stimulation ex vivo, MSDCs from GVHD recipients were significantly much suppressive compared to recipients without GVHD. Moreover, adding functional MDSCs in donor graft alleviated GVHD, whereas partial depletion of MDSCs in vivo using all-trans retinoic acid exacerbated GVHD(Figure 1A and B). These results indicate MDSCs may serve as a biomarker for acute GVHD and tumor relapse after allogeneic BMT. The accumulated MDSCs are not sufficient to completely prevent GVHD although they do ameliorate GVHD. Hence, manipulating MDSCs could be implicated in allogeneic BMT for controlling GVHD or tumor relapse. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

EBV Related Lymphoproliferative Disorders Post Allogeneic Bone Marrow Transplantation for Haematological Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5480-5480
Author(s):  
A. Paisiou ◽  
C. M. Vadikolia ◽  
K. Stefanaki ◽  
E. Goussetis ◽  
I. Peristeri ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Haematological Malignancies ◽  
Hla Antigen ◽  
Post Transplant ◽  
Concurrent Infections

Abstract Background: Post transplant lymphoproliferative disorder (PTLD) is a heterogeneous complication of HSCT. It comprises a spectrum of pathogenetic mechanisms and clinical manifestations. It is mostly associated with EBV infection, either as a consequence of reactivation in the post transplant period or less frequently from primary infection. WHO classification defines four major histopathologic subtypes: 1. early plasmacytic hyperplasia and infectious mononucleosis (IM)-like 2. polymorphic lesions which may be polyclonal or focally monoclonal (P-PTLD) 3. monomorphic lesions that fulfill criteria for aggressive B- or T/NL-cell neoplasm (M-PTLD) 4. classic Hodgkin-type Lymphomas (CHL-PTLD). Indistinguishable categories, such as Hodgkin-like P-or M-PTLD might represent laborious diagnostic dilemmas. In literature, PTLD occurs in less than 1% of non T-cell-depleted grafts from matched siblings compared with as high as 25% in unrelated donor (VUD) recipients. There are several risk factors such as the type of conditioning and the use of ATG, the degree of immunosuppression and complications such as concurrent infections and GvHD. Objectives: To present our experience regarding the frequency, presentation and outcome of EBV related PTLD in a paediatric population of allo-HSCT recipients with haematological malignancies, to assess the risk factors and inquire into the heterogeneity in clinical presentation and outcome. Patients-Methods: From January 2004 until December 2014, 177 allo-HSCTs for myeloid and lymphoid malignancies were performed in patients aged 3 months to 19 years. PTLD was recorded in 15 (8 male) with median age of 13.24 yrs (range 5.0-17.9yrs). 11 patients had VUD, 4 patients had an haploidentical related donor and the grafts depleted of T-cells. 12 patients had peripheral blood and 3 had bone marrow as the source of HSCs. 4 were given a fully matched graft, 6 had 1 HLA antigen or allele mismatched donors, 1 patient had a 2 HLA antigen mismatched donor and 4 had 5/10 HLA matched haploidentical donors. All except for 2 patients were EBV IgG positive and the two seronegative patients had an EBV IgG positive donor. The conditioning regimens used were Busulfan or Treosulfan based in 11 patients with the addition of a combination of Cyclophosphamide, Fludarabine, Melphalan, VP16 and ATG. The latter was administered to all patients. GvHD prophylaxis consisted of Cyclosporin A and Methotrexate. Five patients (1 male) are alive and well with a median follow up of 43.1 months (range 8.3-69.2). Results: Neutrophil and platelet engraftment occurred at a median of 20 (range 14-24) and 21 days (range 14-48) respectively. Acute GvHD (stage II-IV) was recorded in 9 patients. Serial quantitative EBV-DNA/ml was employed routinely and the median day of confirmation of a rising level above 1.0x103/ml was day +58 post transplant. Median EBV copies at diagnosis were 2.3x104/ml(range 1.3x103/ml-2.15x105/ml). EBV positivity was immediately recorded post DLI in 3 patients and reactivation occurred post subsequent DLI. Immune reconstitution had not been achieved in any patient at the time of diagnosis. Median WBC count was 4.1x109/lt (1.04X109/lt - 8.78x109/lt) and all patients had absolute lymphopenia. 9 patients had documented other viral and/or bacterial infections. 2 patients developed M-PTLD, consistent unequivocally with DLBCL, 7 patients had P-PTLD and 6 patients had IM-like PTLD with plasmacytic hyperplasia only. All had anti-CD20, two patients had additional chemotherapy. Although responsive to EBV treatment, 3 died of primary disease recurrence while PTLD failed to regress in 7 patients who died of a multitude of complications. With a median follow up of 43,1 months (range 8.3-69.2), 5 patients (1 male) are alive and well. Conclusions: Nearly all HSCT recipients are EBV infected or will be infected eventually, yet only a fraction develop EBV driven PTLD. In our population the incidence was found to be 8.47%. PTLD exhibits a spectrum of features ranging from non specific and reactive to life threatening, indistinguishable from lymphoma. Administration of ATG, the type and extend of HLA mismatch, multiple sites of disease, immune suppression and concurrent infections heighten the risk of systemic manifestation. Rising EBV loads are strongly associated with impending PTLD, which can occur even with an overall modest viral load, thus requiring prompt recognition and early intervention. Disclosures No relevant conflicts of interest to declare.

scholarly journals Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation

2012 ◽  
Vol 209 (5) ◽  
pp. 903-911 ◽  
Author(s):  
Robert R. Jenq ◽  
Carles Ubeda ◽  
Ying Taur ◽  
Clarissa C. Menezes ◽  
Raya Khanin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Intestinal Inflammation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Allogeneic Bmt ◽  
Initial Onset ◽  
Human Flora

Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.

scholarly journals Host Reactive Donor T Cells Are Associated With Lung Injury After Experimental Allogeneic Bone Marrow Transplantation

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2571-2580 ◽  
Author(s):  
Kenneth R. Cooke ◽  
Werner Krenger ◽  
Geoff Hill ◽  
Thomas R. Martin ◽  
Lester Kobzik ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
Lung Injury ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Allogeneic Bmt ◽  
Donor T Cells ◽  
Ifn Γ

Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear. Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell–depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (Vβ6+and Vβ3+) T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon-γ (IFN-γ) to host antigens in vitro. These in vitro responses correlated with increased IFN-γ and tumor necrosis factor-α (TNF-α) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent.

scholarly journals Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 649-653 ◽  
Author(s):  
RJ Jones ◽  
RF Ambinder ◽  
S Piantadosi ◽  
GW Santos
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Salvage Therapy ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Event Free Survival ◽  
Free Survival ◽  
Allogeneic Bmt

The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established. However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated. We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts. The median age was 26 years in both the allogeneic and the autologous graft recipients. The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001). Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT. The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT. However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8). The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease. Allogeneic BMT appears to induce a clinically significant graft-versus- lymphoma effect. The magnitude of this effect is similar to that reported against leukemias.

scholarly journals Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1933-1939 ◽  
Author(s):  
P Tiberghien ◽  
V Laithier ◽  
M Mabed ◽  
E Racadot ◽  
CW Reynolds ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Marrow Cell ◽  
Interleukin 1 ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Allogeneic Bmt ◽  
Lethal Irradiation

Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment.

Comparative Outcomes of T-Cell–Depleted and Non–T-Cell–Depleted Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia: Impact of Donor Lymphocyte Infusion

1999 ◽  
Vol 17 (2) ◽  
pp. 561-561 ◽  
Author(s):  
Laurie H. Sehn ◽  
Edwin P. Alyea ◽  
Edie Weller ◽  
Christine Canning ◽  
Stephanie Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Complete Remission ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Donor Lymphocyte Infusion ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Allogeneic Bmt

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell–depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+-TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.

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