Age does not adversely influence outcomes among patients older than 60 years who undergo allogeneic hematopoietic stem cell transplant for AML and myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60-75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III-IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9-27.5%) and 54.1% (95% CI, 46.0-61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8-32.3%), 53.3% (95% CI, 46.1-61.7%), 21.4% (95% CI, 15.4-28.1%) and 56.4% (95% CI, 49.2-54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P<0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P<0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort.

Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.

Low-dose antithymocyte globulin enhanced the efficacy of tacrolimus and mycophenolate for GVHD prophylaxis in recipients of unrelated SCT.

We performed a retrospective analysis of the outcome of 197 consecutive unrelated donor transplant recipients who received GVHD prophylaxis either TM regimen (tacrolimus and mycophenolate) (121 patients) or TM/ATG-G regimen (TM with low-dose antithymocyte globulin (ATG) of 4.5 mg/kg, ATG-G, Genzyme) (76 patients). Cumulative incidences of grade II-IV acute GVHD for the TM and TM/ATG-G cohorts were 49% and 61% (P=0.11) and grade III-IV acute GVHD for the TM and TM/ATG-G cohorts were 27% and 14% (P=0.02), respectively. There was no difference in the incidence of relapse or disease progression between TM and TM/ATG-G-16% and 23% (P=0.64). TM/ATG-G cohort had lower incidence of non-relapse mortality (NRM; 37% vs 20%, P=0.01), chronic GVHD (56% vs 43%, P<0.001) and more favorable global chronic GVHD severity (P<0.001). Univariate analyses showed improved OS and PFS of patients who received TM/ATG-G. Multivariate analysis confirmed TM/ATG-G had a favorable influence on OS (P=0.05) but not on PFS (P=0.07). We concluded that low-dose ATG of 4.5 mg/kg given in conjunction with TM improved GVHD prophylaxis without increased risk of relapse. Lower NRM, lower incidence and severity of chronic GVHD could potentially improve survival.

Long-term follow up of patients proceeding to transplant using plerixafor mobilized stem cells and incidence of secondary myelodysplastic syndrome/AML.

We report the long-term follow up of 49 patients (pts) enrolled on plerixafor compassionate use protocol. Thirty-seven pts (76%) had failed one previous mobilization attempt, while 12 (24%) had failed two or more previous attempts. Using the combination of plerixafor and granulocyte colony-stimulating factor, we collected2.5 × 10(6) CD34+cells/kg in 33 pts (67%). Forty-three of the 49 pts proceeded to an auto-SCT (ASCT). The median days to WBC and platelet engraftment were 11 (range, 9-13 days) and 16 (range, 11-77 days) days post ASCT, respectively. The median WBC count, Hb and platelet counts 1 year after ASCT were 4.7 × 10(9)/L, 12.2 g/dL and 109 × 10(9)/L, respectively. With median follow up of 42 months (range <1-54 months), 21 pts had evidence of disease progression. Five pts developed myelodysplastic syndrome (MDS)/AML at median of 29 months post ASCT. The cumulative incidence of MDS/AML at 42 months was 17% (95% confidence interval, 6 to 32%). Development of secondary MDS/AML in pts proceeding to ASCT after plerixafor mobilization needs to be studied further in a larger cohort.

SU-E-T-439: First Experience of Three Dimensional Conformai Radiotherapy (3DCRT) Planning with Helical Tomotherapy.

PURPOSE: A three-dimensional conformal radiotherapy (3DCRT) has been recently introduced to helical tomotherapy, allowing the user to plan and treat patients that do not require sophisticated IMRT planning and delivery. This study aims to test treatment planning on this modality and evaluate its performance by comparing to conventional LINAC-based 3DCRT planning. METHODS: Four clinical cases (whole brain, extremity, lung, and partial breast irradiation) were retrospectively selected from a Pinnacle planning system (Philips Medical System, Fitchburg, WI) and planned on Tomotherapy (Accuray Inc., Sunnyvale, CA). Computed tomography (CT) images together with contours of target and critical structures were exported from Pinnacle to the Tomotherapy planning station. The same prescription and fractionation scheme was adopted. The pitch factor for all clinical cases was set to 0.287. A 2.5 cm jaw was employed except in the lung case the field size was set to 1.0 cm for better dose conformity. The dose grid size was chosen to be half of that of the planning CT images. On Pinnacle 100% prescription dose was delivered to the treatment isocenter while onTomotherapy it was stipulated that at least 95% of the target volume received the prescribed dose. Comparison between two planning strategies was performed, in terms of dose volume histograms (DVH), dosimetric and radiobiological parameters, for plan quality assessment. RESULTS: Comparison of DVHs reveals that up to 25% healthy tissue sparing in volume can be accomplished with Tomotherapy 3DCRT while the same target coverage is ensured. Dosimetric and radiobiological indices between Tomotherapy and Pinnacle planning agree to within 3.0%. Additional beam modifiers and non-coplanar beams associated with LINAC-based 3DCRT are not needed on Tomotherapy, making it more favorable. CONCLUSIONS: Tomotherapy 3DCRT has similar dosimetric performance when compared to conventional LINAC-based 3DCRT while it is substantially easier to use.

Comparative analysis of BU and CY versus CY and TBI in full intensity unrelated marrow donor transplantation for AML, CML and myelodysplasia.

We retrospectively compared clinical outcomes in 1593 T-replete unrelated donor (URD) marrow transplant recipients with AML, MDS and CML who received myeloablative conditioning regimens of either BU and CY (BuCy), standard-dose Cy/TBI (1000-1260 cGy) or high-dose Cy/TBI (1320-1500 cGy). Subjects were drawn from patients transplanted between 1991 and 1999 facilitated by the National Marrow Donor Program. Patients who received high-dose Cy/TBI regimens were slightly younger, more likely to receive a mismatched transplant and to have intermediate or advanced disease compared with patients in the BuCy or standard-dose TBI group. Neutrophil recovery was significantly higher in the standard-dose CY/TBI group compared with the high-dose Cy/TBI or BuCy group. Patients who received the high-dose Cy/TBI regimen had an increased risk of developing grades III-IV aGVHD when compared with the control group who received BuCy (P = 0.011). OS, disease-free survival (DFS), TRM and relapse were not significantly different between any of the regimens. We conclude that BuCy, standard-dose and high-dose Cy/TBI regimens have equivalent efficacy profiles for OS, DFS, TRM and relapse risk in patients undergoing T-replete URD marrow transplantation for AML, CML and MDS.

Clinical feasibility of TBI with helical tomotherapy.

Our purpose was to present the clinical feasibility of TBI with helical tomotherapy (HT) in four patients with AML. Treatment planning, delivery, dose verification and summation, toxicity and patient outcomes for each patient are presented. TBI prescription was set in such a manner that 80% of the clinical target volume received 12 Gy in six fractions, at two fractions per day. Dose reconstruction was carried out by recontouring the regions of interest in the daily pretreatment megavoltage computed tomography of each individual fraction and calculating its corresponding dose. A deformable registration model was used for dose summation of all individual fractions. Differences between planned and delivered doses were calculated. Average planned and delivered doses to the regions of interest differed by up to 2.7%. TBI toxicity was limited to radiotherapy oncology group grade 1 dermatitis in all patients and grade 1 headache in one patient. Two patients are alive with no evidence of disease and no GVHD. Two patients died of GVHD, but there was no evidence of disease at the time of death. We conclude that HT simplifies the process of TBI. Dose verification is possible with HT showing small differences between plan and delivered doses.

Large pericardial effusion as a complication in adults undergoing SCT.

Large pericardial effusion (LPE) leading to cardiac tamponade is a rare complication described in patients undergoing SCT. This complication is considered to be a manifestation of chronic GVHD; however its pathophysiology is poorly understood. Currently, there are no published data systematically describing the incidence, clinical characteristics and outcomes of LPEs in adult stem cell transplant recipients. We retrospectively evaluated 858 adult patients (512 autologous, 148 related and 198 unrelated donor) who underwent hematopoietic stem cell and BM transplants at our institution from 2005 to 2008 for the development of post transplant LPE. Seven patients (0.8%) were found to have LPEs and all these patients had undergone unrelated allografts. The median day of diagnosis post transplant was 229 (range 42-525). None of these patients had active manifestations of GVHD other than serositis at the time of LPE detection. Pericardial window (PW) was successfully placed in all patients who developed cardiac tamponade and most patients with LPE were effectively treated by increasing immunosuppression. We conclude that LPE is a rare late complication after allogeneic transplant in adults and in our study developed only after unrelated transplant. PW can be safely performed in these patients and LPEs can be successfully treated with intensification of systemic immunosupression.

Micafungin alone or in combination with other systemic antifungal therapies in hematopoietic stem cell transplant recipients with invasive aspergillosis.

We describe herein 98 hematopoietic stem cell transplant (HSCT) recipients with invasive aspergillosis (IA) (refractory in 83) who received micafungin either alone (8 patients) or in combination with other licensed antifungal therapies (OLAT) (90 patients). Of the 8 monotherapy patients, 4 were failing OLAT, received de novo micafungin, or were intolerant to prior OLAT (2 patients each). Of the 90 patients treated with combination, 7 had de novo IA and 83 had refractory infection. Most patients (81) had pulmonary IA, 42 (43%) had graft-versus-host disease (GVHD), and 26 (27%) were neutropenic (absolute neutrophil count <500 cells/mm(3)) at onset of treatment. Successful response was seen in 25/98 (26%); an additional 12 patients achieved stable disease. Response was seen in 2/9 (22%) in de novo treatment, 21/87 (24%) in refractory patients, and 2/2 (100%) in toxicity failure patients. Additionally, response was seen in 22 of the 90 (24%) patients treated with combination therapy, and in 3 of 8 (38%) patients who were treated with micafungin alone. No significant differences in responses were found based on type of HSCT, GVHD status, site of IA, or Aspergillus species, and no significant toxicity was seen. Micafungin was well tolerated, even at high doses, and is a reasonable option for treatment of IA in this high-risk patient population.

Modeling of carbon fiber couch attenuation properties with a commercial treatment planning system.

The purpose of this work is to evaluate the modeling of carbon fiber couch attenuation properties with a commercial treatment planning system (TPS, Pinnacle3, v8.0d). A carbon fiber couch (Brain-Lab) was incorporated into the TPS by automatic contouring of all transverse CT slices. The couch shape and dimensions were set according to the vendor specifications. The couch composition was realized by assigning appropriate densities to the delineated contours. The couch modeling by the TPS was validated by absolute dosimetric measurements. A phantom consisting of several solid water slabs was CT scanned, the CT data set was imported into the TPS, and the carbon fiber couch was auto-contoured. Open (unblocked) field plans for different gantry angles and field sizes were generated. The doses to a point at 3 cm depth, placed at the linac isocenter, were computed. The phantom was irradiated according to the dose calculation setup and doses were measured with an ion chamber. In addition, percent depth dose (PDD) curves were computed as well as measured with radiographic film. The calculated and measured doses, transmissions, and PDDs were cross-compared. Doses for several posterior fields (0 degree, 30 degrees, 50 degrees, 75 degrees, 83 degrees) were calculated for 6 and 18 MV photon beams. For model validation a nominal field size of 10 x 10 cm2 was chosen and 100 MU were delivered for each portal. The largest difference between computed and measured doses for those posterior fields was within 1.7%. A comparison between computed and measured transmissions for the aforementioned fields was performed and the results were found to agree within 1.1%. The differences between computed and measured doses for different field sizes, ranging from 5 x 5 cm2 to 25 x 25 cm2 in 5 cm increments, were within 2%. Measured and computed PDD curves with and without the couch agree from the surface up to 30 cm depth. The PDDs indicate a surface dose increase resulting from the carbon fiber couch field modification. The carbon fiber couch attenuation for individual posterior oblique fields (75 degrees) can be in excess of 8% depending on the beam energy and field size. When the couch is contoured in Pinnacle3 its attenuation properties are modeled to within 1.7% with respect to measurements. These results demonstrate that appropriate contouring together with relevant density information for the contours is sufficient for adequate modeling of carbon fiber supporting devices by modern commercial treatment planning systems.

Nephrotic syndrome associated with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Chronic graft-versus-host disease (cGVHD) is the most common late complication of allogeneic hematopoietic cell transplantation (HCT) causing significant morbidity and mortality. The kidneys are not considered a target organ for cGVHD in humans, although animal models show renal damage. Renal involvement in patients with cGVHD, presenting as nephrotic syndrome (NS), has rarely been reported in patients who received allogeneic transplantation. Herein we describe, by far, the largest series of nine patients with NS associated with cGVHD, including two patients who received a reduced-intensity regimen. Pathological features of membranous nephropathy were the most common finding on renal biopsy. The clinical course of the NS was temporally associated with the classical features of cGVHD in all but one of the nine cases. The clinicopathologic features of NS in our series as well as reports in the literature demonstrate an immunopathologic process typical of antibody-mediated damage consistent with cGVHD. Treatment directed against antibody-mediated damage, such as anti-B-cell antibody may play an important role in ameliorating NS associated with cGVHD.

Do negative or positive emotions differentially impact mortality after adult stem cell transplant?

Multiple diverse biomedical variables have been shown to affect outcome after hematopoietic stem cell transplantation (HSCT). Whether psychosocial variables should be added to the list is controversial. Some empirical reports have fueled skepticism about the relationship between behavioral variables and HSCT survival. Most of these reports have methodological shortcomings. Their samples were small in size and included heterogeneous patient populations with different malignant disease and disease stages. Most data analyses did not control adequately for biomedical factors using multivariate analyses. The pre-transplant evaluations differed from study to study, making cross-study generalizations difficult. Nevertheless, a few recently published studies challenge this skepticism, and provide evidence for deleterious effects of depressive symptomatology on HSCT outcome. This mini review integrates the new data with previously reviewed data, focusing on the differential impact of negative and positive emotional profiles on survival. Pre-transplant negative emotional profiles are associated with worse survival in the long term, whereas pre-transplant optimism about transplant appears to affect survival in the short term. These data have practical implications for transplant teams. Pre-transplant psychological evaluation should assess for specific adverse behavioral risk factors, particularly higher levels of depression and lower levels of optimistic expectations about transplant. Transplant centers should develop collaborative studies to further test the effects of these adverse behavioral risk factors, and run multicenter hypothesis-driven clinical trials of psychological intervention protocols. Such studies should aim to better define pragmatics of assessment and intervention (timing, assessment tools, personnel), and evaluate their contribution to improving outcome after transplant.

Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes.

We report long-term outcomes for allogeneic peripheral blood stem cell (PBSC) recipients, evaluating cumulative incidence (CI) of acute and chronic graft-versus-host disease (GVHD), after use of tacrolimus with or without minidose methotrexate for GVHD prophylaxis. From April 1996 to April 1998, 97 adults underwent allogeneic PBSC transplantation. The first 49 received tacrolimus monotherapy as GVHD prophylaxis and the subsequent 48 received combination therapy. The median follow-up for survivors was 67 months. Compared to combination therapy, tacrolimus monotherapy resulted in enhanced neutrophil engraftment, shortened hospitalization, comparable rates of GVHD, and equivalent 100-day survival. The CI of grades II-IV acute GVHD was 35% with tacrolimus and 23% with the combination (P=0.19). The CI of III-IV GVHD was 22% for tacrolimus and 19% for the combination. CI of chronic GVHD was similar between the two groups (P=0.5). Patients with good-risk disease had superior overall survival (OS) when compared to those with poor-risk features (P<0.001). Within the good-risk disease category, patients receiving methotrexate had a trend towards improved OS (P=0.07). Multivariate analysis indicated good-risk disease status and methotrexate were independently associated with improved OS, progression-free survival (PFS), and relapse. In addition, patients developing chronic GVHD had a significantly reduced risk of relapse and improved PFS.

Preferential expression of hPGFS in primary SCCHN and tumour cell lines derived from respiratory and digestive organs.

Identifying overexpressed genes in tumours is a critical step for tumour diagnosis, prognosis, and treatment. Using differential display polymerase chain reaction, sequence analysis, and gene Blast searches, we discovered that human prostaglandin F synthase (hPGFS) was upregulated in squamous cell carcinoma of the head and neck (SCCHN). Northern blot analysis indicated that up to a 16-fold increase in the level of hPGFS expression was detected in 40.5% (15 out of 37) of SCCHN primary tumours. The increased expression of hPGFS in SCCHN was primarily detected in SCC of larynx and hypopharynx (59%, P<0.05). Using the same primary tissue samples, increased levels of epidermal growth factor receptor (EGFR) expression were detected in only 32% of tumour tissues, suggesting hPGFS may have the potential to become a drug target or molecular marker for SCCHN. To determine if the increased level of hPGFS expression came from tumour cells, we determined the level of hPGFS expression in SCCHN tumour cell lines. A high level of hPGFS expression was detected in four out of five tumour SCCHN cell lines. To determine if upregulation of hPGFS is SCCHN-specific, hPGFS expression was analysed in 59 tumour cell lines derived from different types of tumours. The expression of hPGFS was increased from two- to 500-fold in a large portion of cell lines derived from lung (five out of nine), colon (five out of seven) as well as head and neck cancer (four out of five). These data link hPGFS expression to tumours located in the respiratory and digestive organs.

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation.

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.

Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma.

The present randomised phase II study was an effort to evaluate single-agent gemcitabine as a first-line systemic treatment of Asian patients with unresectable hepatocellular carcinoma (HCC). Gemcitabine was given via intravenous infusion at 1250 mg m(-2) on days 1 and 8 of 3-week cycles. Patients were randomised to receive gemcitabine as a 30-min intravenous infusion (standard schedule) or at a fixed dose rate (FDR) of 10 mg m(-2) min(-1). A total of 50 patients were enrolled in the study, of whom 48 received study therapy. One patient on standard schedule had a partial response, for an overall response rate of 2.1% (95% CI: 0.05-11.1%). The median time to progression and survival time were 46 and 97 days, respectively. The overall rates of Grade 3 or 4 haematological and nonhaematological toxicities were 39.6 and 64.6%, respectively, with no significant difference between the two treatment arms. There were no drug-related deaths and severe clinical toxicities were rare. Both schedules of gemcitabine were safe and toxicity was well manageable in this patient population. However, gemcitabine seems no more active than other cytotoxic agents when used alone for systemic treatment of advanced HCC.

Clinical protocol. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma.

High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.

Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age.

The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and disease-free survival, acute and chronic graft-versus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Five-year overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%; P <.0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-matched volunteer donors.

Chronic graft-versus-host disease: clinical manifestation and therapy.

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in long-term survivors of allogeneic stem cell transplantation. The immunopathogenesis of chronic GVHD is, in part, TH-2 mediated, resulting in a syndrome of immunodeficiency and an autoimmune disorder. The most important risk factor for chronic GVHD is prior history of acute GVHD and strategies that prevent acute GVHD also decrease the risk of chronic GVHD. Other important risk factors are the use of a non-T cell-depleted graft, and older age of donor and recipient. Whether recipients of peripheral blood stem cells are at increased risk of chronic GVHD remains unsettled. There are no known pharmacologic agents which can specifically prevent development of chronic GVHD. Agents which have efficacy in the treatment of autoimmune disorders have been utilized as therapy for established chronic GVHD and are associated with response rates of 20% to 80%. Most responses are confined to skin, soft tissue, oral mucosa and occasionally liver. Bronchiolitis obliterans responds infrequently to therapy and is associated with a dismal prognosis. Newer, promising therapeutic strategies under investigation include thalidomide, photopheresis therapy, anti-tumor necrosis factor and B cell depletion with anti-CD20 monoclonal antibody.