Portal vein embolization and application of autologous stem cells in patients with primary unresectable liver tumours.

BACKGROUND: Only 15-20 % of patients with liver tumours can undergo radical surgery. Insufficient future liver remnant volume (FLRV) is one of the main causes of tumours unresectability. Portal vein embolization (PVE) together with administration of haematopoietic stem cells (HSC) may expand the operability of primary unresectable liver tumours. METHODS: In this pilot study, the authors reported on five patients (1 hepatocellular carcinoma, 4 colorectal cancer metastases) with FLRV <30 %, who underwent PVE on the side of the tumour with a subsequent application of HSC to the non-embolized branch of portal vein. RESULTS: PVE with HSC application was without any complications. In three patients, a sufficient increase of FLRV occurred within 2-4 weeks followed by a liver resection. All patients were between 5-12 months after the surgery in good condition; one of them was diagnosed with pulmonary metastasis after nine months that was successfully treated with laser metastasectomy. In one patient with hepatocellular carcinoma, an increase of FLRV and progression of the tumour in the liver occurred following the PVE with administration of HSC and the patient was treated only symptomatically. Despite an adequate increase of FLRV, severe intraabdominal adhesions hampered liver resection in one patient. CONCLUSIONS: Combination of PVE with HSC administration appeared to be a promising method that stimulated growth of FLRV with a subsequent possibility of an early radical liver resection. The issue is a danger of tumour progression in the liver parenchyma following the PVE with HSC. The current randomized study should answer these questions (Tab. 1, Fig. 4, Ref. 38).

[Spontaneous remission of acute myeloid leukemia - a single center case reports]. / Spontánní remise akutní myeloidní leukemie - klinické prípady jednoho centra.

BACKGROUND: Acute myeloid leukemia is a malignant disease characterized by clonal expansion of immature hematopoietic cells - myeloblasts - in the bone marrow. Intensive chemotherapy treatment in elderly patients (over 60) has disappointing results. In these patients, conservative treatment, including compensation of deficiency of red blood cells and platelets by transfusions and treatment of infectious complications is recommended. Also, relatively new treatment with hypometyl agents (azacytidine, decitabine) could be used. DESIGN: The idea of this article is to present a spontaneous remission phenomenon, which has not been published in Czech literature yet. In this article, we present 2 case studies of our patients who were diagnosed with acute myeloid leukemia, were not treated with chemotherapy and spontaneously reached remission of acute myeloid leukemia. CONCLUSION: The mechanisms of the spontaneous remission remain unclear, but we assume positive effect of a severe systemic infection or previous applications of blood transfusions. Antibodies in blood transfusions and a strong immune response to sepsis may have contributed to spontaneous remission.

CD34⁺ cell content in unrelated allogeneic peripheral blood stem cell grafts transported internationally. Does the inter-laboratory variability affect comparability of graft quality data?

BACKGROUND: Increasing numbers of unrelated hematopoietic stem cell grafts are transported internationally and evaluated concurrently in different laboratories. The graft quality assessment using the CD34(+) enumeration could be influenced by inter-laboratory variability. METHODS: We retrospectively analyzed the content of CD34(+) cells in 154 consecutive collections being performed in different transplant centers during two periods (2003-2004, 2007-2010). All samples were tested twice in our own and partner laboratories. CD34(+) percentage and absolute number were compared. RESULTS: The percentage and the total CD34(+) content correlated well in both observed periods (CD34(+)%: r=0.899 and r=0.922; CD34(+)×10(8)/kg: r=0.966 and r=0.880; p<0.0001). Median CD34(+) percentages obtained in our centre in comparison with other laboratories were 0.54% vs. 0.46% in 2003-2004 and 0.69% vs. 0.70% in 2007-2010 period. The degree of laboratory compliance was affected by the laboratory identity. CD34(+) percentage reported by one laboratory and CD34(+)×10(8)/kg reported by three from twelve laboratories lacked statistically significant correlation with our own data. CONCLUSIONS: The study documented that results of CD34(+) cell dose assessment of the same grafts reported by different transplant centers are comparable. The graft quality data and the CD34(+) enumeration possess a limited level of inter-laboratory variability.

[Angioimmunoblastic T-cell lymphoma as a very poor-prognosis malignancy--a single centre experience]. / Angioimunoblastický T-lymfom (AITL) jako velmi nepríznivá malignita - zkusenost centra.

BACKGROUND: Angioimmunoblastic T-lymphoma (AITL) is a poor prognosis malignancy. Because of relatively rare incidence and lack of publications in Czech, we decided to share our experience. PATIENTS AND METHODS: Retrospective analysis of newly diagnosed AITL patients treated at our institution between 1/2000-12/2010. RESULTS: Twelve patients with median age of 64 (43-82) years were analysed. Two patients over 80 years were treated with corticosteroids. Ten patients were treated with 6 cycles of CHOP-21 chemotherapy resulting in: 2/10 (20%) stable disease, 5/10 (50%) partial remission and 3/10 (30%) complete remission. The median EFS and OS of chemotherapy-treated patients were 8 and 10 months, resp. The EFS and OS were both significantly longer in patients who achieved complete remission within the first line of CHOP or autologous stem cells transplantation therapy: 43 vs 6 (p = 0.0052) and 46 vs 6 months (p = 0.0023), respectively. It was not possible to perform autologous transplantation in 4/7 (57%) patients in need for further reduction of the disease because of poor performance status or early progression of lymphoma and death during salvage chemotherapy. CONCLUSION: AITL is a poor prognosis malignancy with a very high risk of early relapse after CHOP induction chemotherapy. In fit patients, autologous transplantation should be performed immediately after induction chemotherapy; information about availability of stem cells donor, both in the family or any available register, should be found during the induction treatment.

[Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient]. / Pacient s B-CLL s anamnézou darování krvetvorných bunek nepríbuznému pacientovi - retrospektivní sledování vývoje nemoci a dusledky pro príjemce.

BACKGROUND: Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. OBSERVATION: In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. CONCLUSION: The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

[The incidence of malignancies and surveillance of hematopoietic stem cells donors--the results of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and Czech National Marrow Donors Registry observation]. / Výskyt malignit a dispenzarizace dárcu krvetvorných bunek--výsledky sledování Hematologicko-onkologického oddelení FN Plzen a Ceského národního registru dárcu drene

BACKGROUNDS: Granulopoesis colony-stimulating factor filgrastim is used to mobilize peripheral stem cells but there are concerns regarding an elevated risk of haematological malignancies. We analyzed the incidence of malignancies and the system of haematopoietic stem cells donor surveillance. PATIENTS AND METHODS: prospective observation of sibling donors of the Haemato-Oncology Department University Hospital in Plzen (Pilsen) and of unrelated donors of the Czech National Marrow Donors Registry (CNMDR) in 2001-2010. RESULTS: No malignancy was observed in a group of 344 unrelated CNMDR donors, providing 753 person-years; one case of chronic lymphocytic leukaemia manifested 6 years after bone marrow donation, with leukaemia clone retrospectively detected by DNA analysis in blood samples taken prior to the marrow donation. Acute myeloid leukaemia, non-Hodgkin lymphoma, renal and colorectal carcinoma were observed in a group of 84 peripheral stem cells sibling donors, providing 337 person-years observation. The respective incidence of the two haematologic malignancies was 593 cases and the expected incidence rate was 143 per 100,000. The sibling (related) donors age was significantly higher: 48 (16-75) vs. 31 (20-42) years, (p<0.0001). Significantly more lost-to-follow-up donors were among the related donors (32% vs. 3%, p<0.0001), even though active surveillance system was implemented. CONCLUSION: The development of malignancies in hematopoietic stem cells donors can naturally be expected. Related (sibling) donors are at higher risk because of their generally older age, and higher susceptibility to haematological malignancies developed within the family. The contribution of filgrastim exposure needs to be further investigated. The follow-up cooperation with related (sibling) donors is limited.

Detection of A B acute lymphoblastic leukaemia blast-specific mutation in HLA-B*39:01.

Human leucocyte antigen (HLA) modifications observed in blast cells in haematologic malignancies can play an important role in disease progression and its therapy. Here we describe an insertion/deletion mutation in the second exon of HLA-B*39:01 that occurred in the blast cells of a patient with B-ALL. This mutation was not present in the nonleukemic cells, in which HLA-B*39:01 was normally expressed.

Determining the extent and stage of disease in patients with newly diagnosed non-Hodgkin's lymphoma using 18F-FDG-PET/CT.

Positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) combined with computed tomography (CT) represents a three-dimensional imaging method suitable for staging in patients with non-Hodgkin's lymphomas (NHLs). The aim of our prospective multicenter study was to assess the value of initial PET/CT as compared with CT and PET alone for determining the stage and extent of the disease. A total of 122 patients with newly diagnosed NHL were examined using PET/CT. Four patients with resected lymphoma lesion and negative PET/CT were therefore excluded from the study. Of the remaining 118 cases, a total of 117 (99%) were described as 18F-FDG-avid. When compared with PET/CT, CT and PET showed very good sensitivity of lymph node imaging (97% and 100%, respectively); the specificity, however, was significantly lower (66.7% and 94.4%, respectively; p=0.0001). When detecting organ lesions, the sensitivity of CT and PET was lower than that of PET/CT (92.5% and 96.3%, respectively; p=0.0001); specificity was significantly decreased in CT and a little lower in PET (59.5% and 91.9%; p=0.0001). When compared with CT alone, PET/CT changed staging of the disease in 11 patients (9%) and was able to detect a total of 82 discrepancies in 67 of the 117 patients (57%). In conclusion, PET/CT is a new standard in imaging the involvement of lymph nodes and extranodal organs in NHL patients regardless of their histopathological types. Both sensitivity and specificity of the examination are higher than those of CT as well as PET alone.

[Treatment of patients with relapsed/refractory Hodgkin lymphoma]. / Lécba pacientu s relabovaným/refraktérním Hodgkinovým lymfomem.

BACKGROUNDS: This retrospective study evaluated treatment outcomes in patients undergoing autologous stem cell transplantation (ASCT) for relapsed/refractory Hodgkin lymphoma (HL). PATIENTS AND METHODS: Overall, 194 HL patients treated with ASCT between 2000 and 2009 were analyzed. Survival was calculated using Kaplan-Meier method and differences in survival between subgroups with log-rank test. RESULTS: Best responses observed after ASCT: 124 complete and 35 partial remissions, 2 patients with stable disease and 33 relapses/progressions. During a median follow-up of 44 months, seventy patients after ASCT progressed/relapsed. Thirty-seven patients received salvage chemotherapy only with or without radiotherapy, 25 underwent allogeneic stem cell transplantation (SCT), 4 the second ASCT and 4 refused treatment. 5-year overall survival after ASCT was 71% and progression-free survival 54%. Median survival of the 70 patients relapsing after ASCT was 16.9 months. Median survival in patients after allogeneic SCT was 31.8 months and 12.4 months in patients treated with other modalities (p = 0.21). Overall mortality was 26.3% (51/194 patients): 13.4% progressions/relapses of HL and 12.9% non-relapse mortality. CONCLUSION: Efficacy of ASCT was confirmed in 54% progression-free survivors. Median survival after ASCT failure is relatively short. There is a slightly longer overall survival after allogeneic SCT, although not statistically significant when compared to other approaches.

Distribution of KIR genes in the population of unrelated individuals homozygous for ancestral haplotype AH8.1 (HLA-A1B8DR3).

Despite the independent segregation of genes encoding killer immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA), there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801-DRB1*0301-DQB1*0201) were genotyped for KIRs. Over all, 14 different genotypes were identified. The KIR genes and genotypes repertoire generally mirror the published frequencies in Caucasians. Except for KIR2DS4, all activating genes presented frequencies below 50%. KIR2DS5 was the least frequent among activating genes (17%), whereas KIR2DL5 (37%) among inhibitory ones. The most frequent (39%) was AA genotype. Twenty-two individuals (54%) had a copy of KIR haplotypes A and B (AB genotype), whereas three (7%) were homozygous for B (BB genotype). Nine of fourteen reported genotypes occurred only in one individual. Five genotypes were reported in less than twenty individuals worldwide and one genotype was reported so far only once. Conversely, the three most frequent genotypes account for 68% of all detected genotypes. The results show the unrestricted KIR diversity in this HLA uniform group and support the fact that the driving force for KIR evolution is not exclusively a major histocompatibility complex.

Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999-2009 in 5 hematology intensive care centers in the Czech Republic.

Acute myeloid leukemia (AML) is a severe condition with a high mortality. When making decisions about the optimal tailor-made therapy, numerous prognostic factors are considered. The study represents a detailed analysis of the role of these factors and treatment outcomes based on a long-term follow-up of patients treated in 5 hematology intensive care centers in the Czech Republic.The studied group comprised 1,188 patients with de novo AML and 328 patients with secondary AML. The latter were significantly older, had more unfavorable cytogenetic changes and less frequently received curative therapy. Curatively treated patients achieved fewer complete remissions and relapsed more often than those with de novo AML. Patients with secondary AML had lower rates of allogeneic transplantation as part of consolidation therapy and a significantly shorter median overall survival. A lower proportion of the patients were alive at the time of analysis. However, the treatment outcome of de novo AML patients is not satisfactory, the only exception being those with acute promyelocytic leukemia. The analysis, which did not evaluate the intention-to-treat criteria and was without randomization, found allogeneic stem cell transplantation to be the most effective modality of consolidation therapy in both groups of patients. .

Reduced-intensity conditioning for allogeneic stem cell transplantation in patients with chronic myeloid leukemia is associated with better overall survival but inferior disease-free survival when compared with myeloablative conditioning - a retrospective study of the Czech National Hematopoietic Stem Cell Transplantation Registry.

Allogeneic stem cell transplantation (AlloSCT) has been currently recommended in the treatment of patients with chronic myeloid leukemia (CML) as a second option after imatinib failure or in selected group of patients with high-risk CML and low risk for transplant-related mortality. The actual role of reduced-intensity conditioning (RIC) before AlloSCT in CML patients has not been yet conclusively established. The Czech National Hematopoietic Stem Cell Transplantation Registry has conducted a retrospective analysis of all patients (n=29) transplanted after RIC from the Registry database containing 295 patients with CML transplanted in the Czech Republic in years 1988-2005 and compared them with patients at comparable age (median age 48.3 and 50.6 years, respectively; p=0.587) transplanted during the same period of time using conventional myeloablative conditioning (n=26). Survival advantage of patients transplanted after RIC has been confirmed by log rank test (p=0.036) despite the fact that the relapse rate was significantly higher in RIC group (44.8% versus 0%). Both groups did not differ significantly in the use of voluntary unrelated donors, type of the grafts and in incidence of acute graft versus host disease (GVHD). However, there were trends for higher risk of CML and higher use of unrelated donors in the myeloablative group while peripheral stem cell grafts and chronic GVHD were observed more frequently in the RIC group. Transplant-related mortality was the leading cause of death in both groups of patients. Our results should be interpreted with caution because they may be influenced by small groups of subjects and also the impact of patients with high EBMT risk score on inferior survival in the myeloablative group cannot be fully eliminated. More retrospective and prospective studies are needed to elucidate the actual role of RIC before AlloSCT for CML.

Is FLT3 internal tandem duplication significant indicator for allogeneic transplantation in acute myeloid leukemia? An analysis of patients from the Czech Acute Leukemia Clinical Register (ALERT).

To assess the prognostic relevance of activating mutations of FLT3 gene on outcome of allogeneic transplantations in AML patients, we performed an analysis of all patients with FLT3 mutations registered in the Czech Acute Leukemia Clinical Register (ALERT) from 2003 till the end of 2005. Within the mentioned period 170 patients with AML of median age 56 years (23-77) were investigated for FLT3 mutation, within them 36 cases (21%) with FLT3 mutations (32 FLT3 ITD and 4 FLT3 D835) were found. Out of FLT3 ITD positive patients 13 had allogeneic transplantation, 20 patients with mutations of FLT3 were treated with chemotherapy without transplantation. Results of the treatment of these patients were compared with the results of the group of patients without FLT3 mutation, which was according to other characteristics identical with the group of patients with FLT3 mutations (n=134). Median overall survival (OS) was significantly shorter for patients with FLT3 ITD (34.8 weeks) than for those without FLT3 mutations (67.7 weeks; P=0.028). Median OS of patients with FLT3 ITD who had allogeneic transplantation was 42.5 weeks; median OS of patients with FLT3 ITD treated only with chemotherapy was 29.6 weeks (P=0.362). After allogeneic transplantation, median OS of FLT3 mutations negative patients was similar to FLT3 ITD positive patients (46.7 versus 42.5 weeks; P=0.443). Our results suggest that at present there is no strong evidence that FLT3 status alone should influence the decision to proceed to allogeneic transplantation in AML patients. Decision to proceed to alogeneic transplantation should not be based on the FLT3 status only, but it should also consider other prognostic factors.

[Allogeneic hematopoietic stem cell transplantation in patients with chronic myeloid leukemia in the Czech Republic--a retrospective analysis of results in years 1988-2005]. / Alogenní transplantace krvetvorných bunek u nemocných s chronickou myeloidni leukemií v Ceské republice: retrospektivní hodnocení výsledku z let 1988 az 2005.

Analyses of hematopoietic stem cell transplantation (SCT) results are of high importance for decision-making on treatment strategy for patients with SCT as a possible therapeutic alternative. In this paper the Czech National Registry of SCT and Transplantation Centre in Pilsen present their joint retrospective analysis of the results of allogeneic SCT in patients with chronic myeloid leukemia (CML) performed in the Czech Republic from 1988 to spring 2005. 295 patients (179 men and 116 women) ranging in age from 6.9 to 59.5 years (median 37.3) underwent transplants. In most cases the donor was an HLA-identical sibling (164; 55.6%) or a voluntary unrelated donor from the register (110; 37.3%), in a minority of cases another relative of the patient (21; 7.1%). Myeloablative conditioning was used in 90% of patients. The source of hematopoietic stem cells was bone marrow in 57%, peripheral blood in 41% and combination of both in 2% of cases. 83.4% of patients underwent transplant in the chronic phase of the illness while 7.8% in the acceleration phase and 6.1% in the blastic phase respectively. The median interval from the diagnosis to SCT was 316 days. Median follow-up after SCT was 2 years. SCT was complicated by acute graft versus host disease of grade II-IV in 33.7% of patients and by chronic graft versus host disease in 36.3% of patients. Median survival was not reached, 18 (6.1%) of patients died due to the relapse of CML and the cause of 101 (34.2%) deaths was transplant-related. Significant trends were observed during the study period: SCT were performed more frequently in older patients, less than one year from the diagnosis, reduced-intensity conditioning was used more often and the source of hematopoietic stem cells was peripheral blood in the majority of patients (p = 0.188 - < 0.0001). Also, transplantation activity changed - the annual rate of SCT increased steadily until 1999, while there was no such an increase between 2000 and 2005. The use of peripheral stem cells was associated with chronic graft versus host disease (p = 0.007). In Cox multivariate analysis the EBMT risk score and the interval from the diagnosis to SCT were identified as independent factors in patient survival. An "ideal" patient, aged under 30, undergoing transplant in the chronic phase of CML within one year since the diagnosis after 2000 had a survival probability of 88% for three years after SCT. It can be concluded that results of allogeneic SCT in CML in the Czech Republic reflect current global trends, are comparable with results achieved in other countries and show significant improvements.

Stem cell transplantation from identical twins in patients with myelodysplastic syndromes.

In a multicentre retrospective EBMT database study, we analysed factors influencing outcome in 38 patients with MDS/sAML who were transplanted with stem cells from their syngeneic twin and compared those to 1444 patients who were transplanted from an HLA-identical sibling. The median time to leukocyte and platelet engraftment was faster in the twin group: 14 vs 17 (P=0.02) and 16 vs 26 days (P=0.09), respectively. The 5 years cumulative incidence of treatment-related mortality (TRM) was higher in the sibling than in the twin group (38 vs 27%; P=0.05). The 5 year cumulative incidence of relapse was 32% (95% CI: 29-35%) for the siblings and 39% (95% CI: 26-60%; P=0.6) for the twins. A trend for better 5-years disease-free and overall survival was observed in the twin group: 34% (95% CI: 14-54%) vs 28% (95% CI: 25-31%; P=0.2) and 36% (95% CI: 15-57%) vs 32% (95% CI: 29-35%; P=0.09), respectively. In a multivariate analysis, stem cell transplantation from identical twins had a lower TRM: HR: 0.4 (95% CI: 0.2-0.9; P=0.03). The relapse rate was similar for both groups with a HR of 1.2 (95% CI: 0.07-2.1; P=0.5), with a better survival for the twins: HR 0.6 (95% CI: 0.4-1.0; P=0.07). We conclude that twin transplantation in MDS/sAML is associated with a similar relapse risk, a lower TRM and a trend for better overall survival in comparison to transplantation from HLA-identical siblings.

Successful treatment of severe Shulman's syndrome by allogeneic bone marrow transplantation.

We describe a patient with severe Shulman's syndrome (ShS) (eosinophilic fasciitis). This auto-immune disease involved not only the skin and muscles, but the bone marrow as well - thereby fulfilling the criteria of severe aplastic anemia. As the disease was steroid-resistant, the patient underwent allogeneic bone marrow transplantation (BMT). Remission of ShS was achieved. Eight months later chronic GVHD developed and relapse of ShS (probably induced by GVHD) occurred. He was successfully treated with corticosteroids and the disappearance of GVHD was followed by cessation of the symptoms of ShS. At present (34 months following BMT) he is doing well and displays no signs of ShS or GVHD. This case suggests that an aggressive immunoablative preparative regimen with subsequent allogeneic BMT can result in long-lasting clinical remission of a severe auto-immune disease.

Successful autologous transplantation in a patient with severe aplastic anemia (SAA).

We report a patient who underwent peripheral blood hematopoietic progenitor (PBHP) autologous transplantation for his third SAA relapse. Although his repeated relapses were always successfully reversed by immunosuppression, he developed anaphylaxis with horse, rabbit and mouse immunoglobulins as a side-effect of his previous treatment. He was mobilized with G-CSF and underwent three leukaphereses in the period of hematologic recovery after the second relapse. Fourteen months later, he suffered his third relapse, rescued by autologous PBHP transplantation after cyclophosphamide and melphalan conditioning. At present he is 15 months after transplantation without any treatment, transfusion-independent and in good condition. Others have published the observation that sufficient PBHP can be collected at least in some patients with SAA. Our experience shows that in repeatedly relapsing SAA with no other treatment options autologous transplantation with previously collected PBHP can result in successful hematologic reconstitution.

Individual criteria could be optimal for starting G-CSF application after autologous stem cell transplantation.

The optimal time for starting G-CSF application after autologous peripheral stem cell transplantation (APSCT) still remains undetermined. All previous studies used 'fixed' days (0 or +1 vs +5 or +7 post-transplant) for this purpose. As many other drugs have individual, patient-dependent criteria (eg antibiotics, blood products, etc), and the discontinuation of G-CSF also has strict patient-dependent criteria (surprisingly absent when starting the drug) we suppose that attempts to find general criteria suitable for every patient may not be successful. In order to also take the patients' individual predispositions into account we designed a randomized clinical trial to compare 'immediate' administration of G-CSF (day +1: group A) vs 'delayed, patient-dependent' (first day when absolute neutrophil count (ANC) was below 0.5 x 10[9]/1: group B) therapy with G-CSF (both groups received 10 microg/kg/day i.v.). A total of 70 patients after APSCT suffering from non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) conditioned with BEAM, or from multiple myeloma (MM) after melphalan (L-PAM: 200 mg/m2) were enrolled in this study (35 in each group). Both groups were comparable with regard to age, sex, disease stage and previous therapy as well as the number of CD34+ cells transplanted. In group B, G-CSF administration began on day +4 post-transplant (+2 - +5). There were no detectable differences seen in the hematopoietic recovery (time to reach ANC more than 0.5 x 10(9)/l: 12 days vs 13 days; time to platelet recovery, more than 50 x 10(9)/l: 24 days in both groups), use of blood products or antibiotics, infections, or days of hospitalization. Delayed G-CSF application led to significant cost saving in terms of APSCT (approximately US$1341 for each patient). We suggest that 'patient-dependent' criteria for starting G-CSF are reasonable especially in patients conditioned with protocols only slowly inducing neutropenia: eg NHL and HD patients after BEAM, MM after L-PAM or patients after busulphan and cyclophosphamide (BUCY2).

Autologous CD34+ cells transplantation after FAMP treatment in a patient with CLL and persisting AIHA: complete remission of lymphoma with control of autoimmune complications.

A 48-year-old male with CLL and concomitant AIHA unresponsive to chlorambucil was treated with fludarabine. The remission of CLL and improvement of the AIHA was achieved, but the patient remained steroid dependent. Therefore, high-dose chemotherapy followed by CD34-selected autologous peripheral blood stem cells transplantation was performed and this led to long-term clinical, immunophenotypic and molecular remission with disappearance of AIHA. Twenty-three months later, the CLL recurred with signs of AIHA. In this patient with AIHA, HDC and selected CD34+ cells completely, though temporarily, controlled both CLL and associated immune complications. This case illustrates the potential application of this approach in the management of CLL patients with immune complications.

Allogeneic BMT in patients above 45 years of age: a single center experience.

Increasing age has been reported to be associated with worse outcome and higher occurrence of complication after allogeneic bone marrow transplantation. We analysed a cohort of 39 patients between the ages of 45 and 57 (median 49 years) with different hematologic malignancies who had undergone BMT in our institution over the preceding 4 years. Pretransplant conditioning consisted of Bu/CY2, GVHD prophylaxis of a combination of cyclosporine and "short" methotrexate. At present 54% of patients remain alive (with a median follow-up 44 months), the probability of survival at 5 years is 53% (5-year DFS 78%). The 5-year survival probability in the control group of younger patients is 53% (P = 0.8003). Main causes of death were GVHD (4 patients, 10%), relapse (5 patients, 13%) and infection (6 patients, 15%). The incidence of acute GVHD grade II-IV was 51% (grade III-IV 0% patients), the incidence of chronic GVHD 49% (limited 18% and extensive 31% patients). Our results suggest that allogeneic BMT can be performed in patients above the age of 45 years with acceptable morbidity and mortality, especially if a family HLA matched donor is available.