Bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with acute myeloid leukaemia, an Acute Leukaemia Working Party analysis in 2262 patients.

BACKGROUND: No survival benefit of using blood stem cells instead of bone marrow (BM) has been shown in matched unrelated donor (MUD) transplantation. DESIGN AND METHODS: In a retrospective registry analysis, we compared the use of blood stem cells (n = 1502) and BM (n = 760) from unrelated donors in patients aged 18-60 years with acute myeloid leukaemia (AML) undergoing myeloablative conditioning between 1997 and 2008. The blood stem cell recipients were older (P < 0.01), had more advanced disease (P < 0.0001) and received less total body irradiation (P < 0.0001) and more antithymocyte globulin (P = 0.01). RESULTS: Recovery of neutrophils and platelets was faster with blood stem cells (P < 0.0001). The incidence of acute graft-versus-host disease (GVHD) was similar, but there was more chronic GVHD in the blood stem cell group [hazard ratio (HR) = 1.29, P = 0.02]. There were no significant differences in nonrelapse mortality (NRM), relapse incidence and leukaemia-free survival (LFS) between the two groups amongst patients with AML in remission. In patients with advanced leukaemia, NRM was lower (HR = 0.61, P = 0.02) and LFS was prolonged (HR = 0.67, P = 0.002) when blood stem cells were used. At 3 years, LFS for all patients, regardless of remission status, was 41% for both treatment groups. The outcome was not affected after multivariable analysis adjusted for confounders. CONCLUSION: Blood stem cells compared with BM in MUD transplantation for patients with AML in remission resulted in the same rates of LFS. In patients with advanced leukaemia, the blood stem cell group had reduced NRM and improved LFS.

Alloreactivity: the Janus-face of hematopoietic stem cell transplantation.

Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.

The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin ß-4, eukaryotic translation initiation factor 4γ2, fibrinogen ß-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.

Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors.

There is consensus that matching of unrelated donors (URD) and patients for HLA class II alleles improves the outcome of hematopoietic stem cell transplantation (HSCT). However, the significance of HLA class I allelic mismatches for transplant outcome is under discussion and reports on long-term effects like chronic graft-versus-host disease (GVHD) are rare. Thus, we investigated the association of human leukocyte antigen (HLA) class I allele mismatches and outcome in 144 patients given HSCT from URD who were matched for HLA-DRB1, DRB3/4/5, and DQB1 alleles. The risk of chronic GVHD was significantly increased in patients with class I mismatched donors, the mismatch either detected by low- or high-resolution typing. A single HLA class I allele mismatch significantly increased the risk of chronic GVHD in multivariate analysis. Overall survival was significantly reduced in patient/donor pairs with more than one-allele class I mismatch. Thus, selection of unrelated donors for transplantation should be based on high-resolution HLA class I typing.

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.

The translocation t(8;16)(p11;p13) is associated with acute myeloid leukemia displaying monocytic differentiation (AML FAB M4/5) and fuses the MOZ (also named MYST3) gene (8p11) with the CBP (also named CREBBP) gene (16p13). Detection of the chimeric RNA fusions has proven difficult; only three studies have described successful amplification of the chimeric MOZ-CBP and CBP-MOZ fusions by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed four cases of AML M4/5 with t(8;16)(p11;p13) by RT-PCR and fluorescence in situ hybridization (FISH) and characterized the reciprocal RNA fusions from three cases. We cloned both genomic translocation breakpoints from one case by long-range PCR and successfully applied RT-PCR to monitor minimal residual disease (MRD) between clinical complete remission and relapse. In three cases, the genomic breakpoints occurred in MOZ intron 16 and CBP intron 2. In one case, no fusion transcript was detected. The available data suggest clustering of t(8;16)(p11;p13) breakpoints in these introns leading to reciprocal in-frame MOZ exon 16/CBP exon 3 and in-frame CBP exon 2/MOZ exon 17 chimeric transcripts in the majority of cases. The described RT-PCR strategy may be valuable both for the routine detection of the t(8;16)(p11;p13) as well as for monitoring of MRD in this prognostically unfavorable patient group.

Treatment of leukemic relapse after allogeneic stem cell transplantation with cytotoreductive chemotherapy and/or immunotherapy or second transplants.

We analyzed toxicity and efficacy of chemotherapy (CT) or second stem cell transplantation (SCT) and/or immunotherapy defined as stop of immunosuppression (IS) or donor leukocyte infusion (DLI) in 47 patients relapsing with acute leukemia. Ten patients received no treatment and 14 patients were treated with CT only. In 12 patients IS was stopped and three of them received additional CT. Five patients received DLI after CT as consolidation and one patient as frontline therapy. Five patients received a second SCT. Median overall survival after relapse was 2 months for the untreated patients, 2 months for patients receiving CT only, 2 months in patients after cessation of IS, 17 months in DLI treated patients and three months in patients receiving a second SCT. Fourteen patients achieved remission after relapse. Two with CT (2, 2 months), three with SI (3, 19, 19+ months), six with DLI (3, 8, 9, 14, 20, 36 months) and three with second SCT (2, 4, 6 months). Conventional CT was able do re-establish donor hematopoiesis and patients achieving remission showed a significantly better survival than patients with refractory disease. Patients who were brought into remission by DLI or cessation of IS had a significantly better survival than patients who achieved remission with CT alone or a second SCT. We conclude that a selected group of patients achieving remission with regeneration of donor hematopoiesis following CT might benefit from immunotherapy as consolidation.

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.

Secondary solid cancer screening following hematopoietic cell transplantation.

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

Streptococcus pneumoniae mycotic aortic aneurysm after allogeneic bone marrow transplantation.

BACKGROUND: Streptococcus pneumoniae (SP) is a common cause of community-acquired pneumonia and accounts for up to 30% of all cases of pneumonia. Patients with chronic graft-versus-host-disease (GvHD) after allogeneic bone marrow transplantation (BMT) have a high susceptibility to SP infections. So far, mycotic aneurysm resulting from SP has not been reported after BMT. METHODS: We report on a patient with extensive, chronic GvHD who developed low back pain 22 months after allogeneic BMT. RESULTS: Computed tomography of the abdomen displayed mycotic, saccular aneurysmatic enlargement of the infrarenal aorta, with leakage of contrast medium into the aneurysm. The aneurysm was resected, and the defect was closed with an autologous patch from the internal iliac artery. Bacteriologic samples from the abscess grew SP. The patient recovered uneventfully. CONCLUSIONS: This observation confirms the importance of pneumococcal prophylaxis after BMT and suggests that an aggressive diagnostic approach should always be considered in patients with chronic GvHD, even if they present with nonspecific symptoms.

Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease.

BACKGROUND: Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). Weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. METHODS: We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. RESULTS: Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. CONCLUSIONS: Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Successful lung transplantation for bronchiolitis obliterans after allogeneic marrow transplantation.

BACKGROUND: Bone marrow transplantation (BMT) is an established therapy for a variety of hematological diseases with curative potential. However, despite improvements in supportive care, pulmonary complications remain a significant cause of morbidity and mortality. METHODS: We report on a patient who received a double lung transplantation (LTX) for therapy-refractory bronchiolitis obliterans (BO) associated with extensive chronic graft-versus-host disease (GVHD) after allogeneic BMT. RESULTS: At present, 38 months after BMT and 23 months after LTX, the patient is in complete hematological and cytogenetic remission and without signs of respiratory distress. CONCLUSIONS: This case illustrates that lung transplantation could be a therapeutic option in selected patients with BO after allogeneic BMT that is associated with extensive chronic GVHD and who are refractory to conventional immunosuppressive therapy.

Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis.

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.

Subdural hygromas after bone marrow transplantation: results of a prospective study.

BACKGROUND: Subdural hygromas after bone marrow transplantation (BMT) have been occasionally found in patients with persisting headache and vomiting. We assessed the incidence of subdural hygromas after BMT and tried to define possible risk factors associated with this complication. METHODS: Fifty bone marrow graft recipients surviving more than 30 days were consecutively enrolled into a prospective study. Cranial CT scans were performed before and 30 days after BMT. Clinical data and symptoms were recorded daily during the first 30 days after BMT. In patients with subdural hygromas, a magnetic resonance imaging scan and monthly follow-up cranial computed tomography scans were performed until fluid collections had resolved completely. RESULTS: In 9 of the 50 patients (18%) who survived 30 days after transplantation, newly acquired subdural hygromas were found. Patients with hygromas suffered significantly longer and more severely from headache and vomiting (P=0.01). Application of intrathecal methotrexate and arterial hypertension occurred significantly more often in patients with hygromas (P=0.01). In a stepwise logistic regression model, arterial hypertension and intrathecal methotrexate application were the only independent risk factors for the development of hygromas. Monthly follow-up cranial computed tomography scans showed that all hygromas resolved completely after a median of 60 days after diagnosis (range: 30-120 days). CONCLUSIONS: Subdural hygromas are a frequent complication after BMT within the first 30 days after transplantation. They are reversible and disappear within 2-3 months. The need for routine application of intrathecal methotrexate in standard risk leukemia patients should be critically addressed. Furthermore, close monitoring of blood pressure and immediate antihypertensive therapy might contribute to avoid formation of subdural hygromas.

Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) embraces disorders characterized by the presence of marrow-derived abnormal Langerhans cells. A small number of patients with multisystem disease, vital organ dysfunction and rapid disease progression are considered to have a poor prognosis despite various treatments. Antiproliferative and immunosuppressive therapy, in combination with marrow transplantation, could be the appropriate treatment for these poor-prognostic patients. Four patients with progressive LCH were treated with high dose chemotherapy and fractionated total body irradiation followed by either an allogeneic (n = 2) or autologous (n = 2) marrow graft. Two of them are alive and have been disease free for almost 2 and 4 years after marrow grafting, respectively. One of the two survivors is the recipient of an allogeneic and the other of an autologous marrow graft. Two patients died, one of intrapulmonary hemorrhage 14 days after transplantation with active disease at autopsy, and the other of relapse of the original disease 355 days after marrow grafting. For patients with multisystem progressive LCH, allogeneic and autologous marrow transplantation may offer an opportunity for long-term remission and disease-free survival.

Influence of human platelet antigen match on the success of stem cell transplantation after myeloablative conditioning.

Mismatches between donor and recipient for human platelet antigens (HPA) may affect the success of transplantation due to: (a) serving as minor histocompa-tibility antigens and therefore render recipients at risk for graft-versus-host disease (GvHD), (b) inhibition of thrombopoiesis due to platelet antibodies. We therefore evaluated the occurrence of GvHD and need of platelet support by prospective analysis of donor-recipient pairs (n=53) for HPA-1, -2, -3, and -5 allotypes and screening for platelet antibodies prior to transplantation and in weekly intervals until day 100 after transplantation. Neither the incidence of GvHD nor the onset of thrombopoiesis, nor the CCI after platelet transfusions, nor the frequency of platelet transfusions was affected by HPA mismatches. Settings of homozygous donors vs heterozygous recipients or homozygous recipients vs heterozygous donors were not associated with any adverse effects on the outcome of the transplantation. Thus, the HPA-match does not affect the success of transplantation.

G-CSF stimulation of donor myelopoiesis prolongs survival of relapsed BCR-ABL-positive acute lymphoblastic leukemia after allogeneic marrow transplantation.

An allogeneic sex-mismatched BMT which was performed in a male patient with BCR-ABL-positive ALL in second hematological and central nervous system relapse resulted in a CR for 12 months. After BMT, the patient was closely monitored with reverse transcription (RT)-PCR. One month before a third relapse RT-PCR became positive. During relapse G-CSF was administered. It specifically stimulated the donor-derived myelopoiesis and led to the stabilization of the disease for 8 months. Fluorescence in situ hybridization analyses of individual cell populations revealed that during the whole course of G-CSF administration granulocytes, CD4+, CD8+ and CD34+/CD10- cells were of female (donor) origin and only the CD34+/CD10+ cells which represented the leukemic blasts, were of male (host) origin.