In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.

BACKGROUND: Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. METHODS: We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells. RESULTS: Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts. CONCLUSIONS: Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.

No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients.

BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.

Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 or TSC2 genes and characterized by slow-growing tumors in multiple organs. Of the affected individuals, 10% display subependymal giant cell astrocytomas (SEGAs), which can lead to substantial neurological morbidity. The TSC1/TSC2 protein complex is a negative regulator of the mTOR pathway. Hence, mutations in these genes in preclinical models are associated with increased mTOR pathway activation and heightened sensitivity to mTOR inhibitors. We hereby report our experience with RAD001 (Everolimus) therapy, a novel mTOR inhibitor, in inducing a dramatic regression of SEGAs. METHODS: A patient with TSC and SEGAs was treated with 10 mg/day oral RAD001. MRIs and neuro-ophthalmological exams were performed before and at regular intervals following the initiation of therapy. RESULTS: The lesions exhibited significant regression in several tumor locations and stabilization in others, accompanied with an improvement of his visual status. Treatment was well tolerated for 11 months but was than discontinued due to hypertension and elevated CPK, without evidence for rhabdomyolysis. Yet, during 9 months following the interruption of therapy, SEGAs remained unchanged. CONCLUSIONS: Oral RAD001 demonstrated preliminary encouraging results as treatment of astrocytomas associated with TSC. These preliminary results were recently supported by the Novartis announcement of the phase II study of RAD001 for SEGAs, which was not published yet. According to their statement, 75% of the patients showed reduction of SEGAs' volume following treatment with RAD001. Based on these results, RAD001 may be an alternative to surgery in selected patients with TSC and SEGAs.

An outbreak of Burkholderia cenocepacia bacteremia in immunocompromised oncology patients.

BACKGROUND: Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. METHODS: A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). RESULTS: Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. CONCLUSIONS: B. cenocepacia is an emerging nosocomial pathogen among oncology patients.

Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila.

The coordinated growth and development of synapses is critical for all aspects of neural circuit function and mutations that disrupt these processes can result in various neurological defects. Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway, regulate synaptic development in vertebrates and invertebrates. At the Drosophila larval neuromuscular junction (NMJ), the retrograde BMP pathway is a part of the machinery that controls NMJ expansion concurrent with larval growth. We sought to determine whether the conserved Hippo pathway, critical for proportional growth in other tissues, also functions in NMJ development. We found that neuronal loss of the serine-threonine protein kinase Tao, a regulator of the Hippo signaling pathway, results in supernumerary boutons which contain a normal density of active zones. Tao is also required for proper synaptic function, as reduction of Tao results in NMJs with decreased evoked excitatory junctional potentials. Surprisingly, Tao function in NMJ growth is independent of the Hippo pathway. Instead, our experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. Taken together, these results support a role for Tao as a novel inhibitor of BMP signaling in motor neurons during synaptic development and function.

Lymphomatous T-cell leukemia in two Arab children. Is there a role for an environmental effect.

Two Arab children from the Gaza strip presented with fever, weakness, hepatosplenomegaly, lymphadenopathy and leukocytosis. The peripheral and bone marrow blasts had an immunophenotype compatable with T-cell acute lymphoblastic leukemia, and exhibited unusual markers (CD2+, CD3+, CD4-, CD8-). Cytogenetic studies revealed t(8;14)(q24;q11), possibly involving the alpha/delta locus of the T-cell receptor gene on chromosome 14 rather than the immunoglobulin heavy-chain locus usually involved in the t(8;14)(q24;q32), which is typical for Burkitt's leukemia/lymphoma. One of the children had a brother who died of T-cell acute lymphoblastic leukemia a few years later, however, his blasts showed deletion of chromosome 12. The possible role for environmental factors associated with low socioeconomic status, as well as of genetic factors in leukemogenesis are discussed.

In vivo clonal evolution of pre-B to B-cell acute lymphoblastic leukemia in childhood.

Two cases are described that provide further evidence for clonal evolution in pre-B-cell acute lymphoblastic leukemia. Two infants, whose lymphoblasts at diagnosis were morphologically subtyped as L1 and immunophenotyped as HLA DR+, CD19+, CD10+/- and C mu-, were induced and maintained in remission. One child relapsed 6 months after initiation of therapy. This time his lymphoblasts had L3 morphology and immunophenotyping demonstrated the appearance of surface immunoglobulins. The second child relapsed 18 months after initiation of therapy with a lymphomatous picture. He also had peripheral and bone marrow blasts with L3 morphology and surface immunoglobulins. A lymph node biopsy showed diffuse small non-cleaved lymphoma with a 'starry sky' appearance compatible with Burkitt's lymphoma. Only one case with a similar clonal evolution has been reported in the literature, but no surface immunoglobulins were demonstrated. The significance of clonal evolution in these cases and its potential practical implications are discussed.

Mutation analysis of the FAS and TNFR apoptotic cascade genes in hematological malignancies.

OBJECTIVE: The existence of properly functioning apoptotic pathways is of utmost importance in the maintenance of a normal cell count. Several groups have searched for mutations in the FAS receptor, a well-characterized apoptotic protein carrying a death domain, and reported the existence of rare mutations in multiple myeloma, T-acute lymphoblastic leukemia (T-ALL), and adult T-cell leukemia. Our aim was to expand these searches by looking for mutations in the death domains of FAS, FADD, TNFR, TRADD, and RIP, in the promoter region of FAS, and in the protease domain of caspase 10, in a larger variety of hematological malignancies, some of which express an apoptosis-resistant phenotype. METHODS: We extracted RNA and DNA samples from 92 hematological malignancies: chronic lymphocytic leukemia (CLL; 31 cases), chronic myelogenous leukemia (CML; 28 cases), essential thrombocythemia (ET; 8 cases), acute lymphocytic leukemia (ALL; 6 cases), acute myeloblastic leukemia (AML; 6 cases), hairy-cell leukemia (HCL; 3 cases), Burkitt's lymphoma (3 cases), polycythemia vera (PV; 3 cases), myelofibrosis (2 cases), and chronic myelomonocytic leukemia (CMML; 2 cases) and performed PCR-SSCP and sequence analysis on these samples. RESULTS: Five polymorphic patterns were found: three in the death domain of the FAS gene in CML patients, one in the promoter of this gene in a CLL patient, and the fifth in the death domain of the TRADD gene in a CML patient. No mutations, altering amino acids, were found in these genes in any of the aforementioned malignancies. CONCLUSIONS: These observations imply that mutations in the death domains of FAS, FADD, TNFR, TRADD, and RIP and in the protease domain of caspase 10 are not a major cause for failure of apoptosis in hematological malignancies, mainly CML and CLL. Regulatory and epigenetic abnormalities in these apoptotic cascade members and aberrations in other components of all death machinery should be looked for.

Hematopoietic stem cell donation: psychological perspectives of pediatric sibling donors and their parents.

Allogeneic stem cell transplantation (SCT) is widely used for treatment of various life-threatening pediatric diseases. It is an intensive process that psychologically affects the whole family. Pediatric donors represent a very unique, underreported, group. The aim of this study is to investigate the sibling donors' and their parents' perspective on the donation process. The cohort included 36 sibling donors and 50 parents of pediatric patients who underwent allogeneic SCT between 1995 and 2010 and were alive at the time of the study. Mean age at donation was 14.78±8.350 years in donors' group and 8.22±4.639 years in parents' group. Data were collected by anonymous questionnaires. Three psychological dimensions were analyzed: donors' personal perspective; donor-recipient interpersonal relationship and the influence of the donation on the family unit. Results showed that the donors experienced a wide range of complex emotional responses, positive and negative, whereas the parents' responses were mainly positive and less complex. This study presents both the sibling donor's and parents' perspective, giving a more complete picture of the donation process within the family. The effects of this intense experience of SCT has a long-term impact on the whole family, indicating the need for follow-up and psychosocial support.

Infectious agents and environmental factors in lymphoid malignancies.

A strong association was found to exist between patterns of lymphoid malignancies and socioeconomic status. B-cell lymphomas and T-acute lymphoblastic leukemia are much more prevalent in developing countries where the chances of acquiring infections especially at a younger age are high. B-cell precursor acute lymphatic leukemia, however, are much more prevalent in the Western world. Many infectious agents are associated with lymphatic malignancies. Epstein-Barr virus is involved in African Burkitt's lymphoma, human immunodeficiency virus-related Burkitt's lymphoma, lymphoproliferative syndrome post-transplantation, and Hodgkin's disease. Other infectious agents which may play a role in lymphoproliferative disorders are human immunodeficiency virus in acquired immune deficiency syndrome-associated lymphoma, human T-lymphotropic virus in adult T-cell lymphoma, Helicobacter pylori in mucosa-associated lymphoid tissue lymphoma, theileriosis in lymphoproliferative syndrome in cattle, Avian leukosis virus in chicken bursal lymphoma, and possibly a bacterial infection in immunoproliferative small intestine disease, potentially reversed by antibiotic therapy. The association between infectious agents and hematologic malignancies may be explained by the creation of large populations of activated cells followed by higher occurrences of 'genetic accidents'. This theory may be reinforced in at least some malignancies with the existence of viral proteins which either have complex relationships with key cellular gene products like p53 and Rb which have roles in cell cycle control, or share common motifs with bc1-2, therefore operating as anti-apoptotic elements. Whenever these genes are deranged, cell deoxysibonucleic acid repair or apoptosis are no longer possible, thereby creating a state of genome instability, increased acquisition of mistakes, and increased chances for malignant transformation.

Soluble interleukin-6 receptors in hematology patients undergoing bone marrow transplantation.

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin (IL)-6, which may display antitumor activity. We evaluated sIL-6R and IL-6 levels in the sera of 24 patients following transplantation (allogeneic, n=17; autologous, n=7). Five patients developed acute graft-versus-host disease (AGVHD), three had early graft rejection, and three had an early relapse following bone marrow transplantation (BMT). Soluble IL-6R levels were evaluated at day - 10, day 0, day of engraftment, and during BMT-related complications, using IL-6R-specific monoclonal antibodies (mAb) and double-sandwich ELISA. In normal controls, sIL-6R and IL-6 levels were 20+/-3 ng/ml and 0.01+/-0.005 ng/ml, respectively. Soluble IL-6R levels increased in direct correlation with engraftment in the uneventful allogeneic transplants (17.7+/-2.1 ng/ml at day 0 to 49.7+/-2.6 ng/ml at day of engraftment, n=6, P<0.05) as well as in the autologous transplants (26.8+/-2.82 at day 0 to 66.4+/-12.9 at day of engraftment, n=5, P=0.01). In contrast, IL-6 levels declined with time during the conditioning period and showed only a modest elevation following BMT. Increased levels of sIL-6R and IL-6 were found in the patients who developed AGVHD (23.8+/-4.2 and 0+/-0 ng/ml at day 0 to 79+/-6.9 and 0.26+/-0.04 ng/ml, respectively, at time of AGVHD, n=5, P=0.01). No correlation was found between the severity of AGVHD and sIL-6R levels. In the three patients with early relapse, sIL-6R levels increased from 30+/-0 ng/ml at day 0 to 90 ng/ml (P=0.05) and IL-6 levels increased from 0 to 0.16+/-0 ng/ml, respectively. The mean elevation of sIL-6R in the patients with early relapse and AGVHD was significantly higher than the mean elevation in the patients with the relatively smooth engraftment (P<0.05). Contrary to these findings, in the three patients with graft rejection, sIL-6R levels decreased while IL-6 was found to be elevated. Basic disease, conditioning regimen, type of transplant, GVHD propylaxis, and T cell depletion had no effect on sIL-6R or IL-6 levels. In summary, sIL-6R levels positively correlated with engraftment. Both sIL-6R and IL-6 levels were found to be significantly elevated in patients who developed AGVHD or early relapse following BMT. Therefore, the sIL-6R level may be used as a tool for assessing engraftment and transplant-related complications following BMT.

Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma.

BACKGROUND: Immunotherapy given post-autologous stem cell transplantation may eliminate residual tumor cells escaping the conditioning protocol. METHODS: Five children suffering from stage IV neuroblastoma were treated by recombinant interleukin-2 (IL-2) post-autologous peripheral blood stem cell transplantation. The patients' peripheral mononuclear cells were monitored for CD3+ and CD56+ levels, their proliferative response and killing of various cell lines targets. RESULTS: An increase in the level of total lymphocytes, mainly due to expansion of T cells, and enhanced proliferative response to phytohemaglutinin were observed. Elevated cytotoxicity against K562 and neuroblastoma target cells was detected in four patients and against K562 targets in one patient. Toxicity included mild thrombocytopenia, and fever in four patients and mild to moderate encephalopathy which necessitated withdrawing one patient from the protocol. Three of five patients studied are alive today, one of them whose IL-2 was stopped, is in relapse. Two patients have died. CONCLUSIONS: Immunotherapy with s.c. intermediate-high dose IL-2 is feasible and results in expansion of T cells and in stimulation of killing activity against several targets including in some cases, neuroblastoma tumor cells.

Solitary pulmonary cholesteroloma, multiple xanthelasmas and lipemia retinalis complicating hypercholesterolemia after bone marrow transplantation.

A 22-year-old female with diffuse mixed T cell lymphoma in second complete remission underwent allogeneic BMT from her HLA-compatible brother. Transplantation was complicated by acute graft-versus-host disease (GVHD), cytomegalovirus (CMV) infection, and combined hepatotoxic/cholestatic liver disease 45 days post-BMT. Cholesterol levels reached 65 mmol/l, and high density lipoprotein (HDL) cholesterol decreased to 0.23 mmol/l. She developed skin xanthelasmas, lipemia retinalis, and a solitary lung lesion, which was clinically diagnosed as pulmonary cholesteroloma. All these complications resolved following plasmapheresis and hypolipidemic treatment with lovastatin and cholesterol levels normalized.

Massive pericardial effusion complicating the course of chronic graft-versus-host disease (cGVHD) in a child with acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

The pathogenesis and clinical features of chronic graft-versus-host disease (cGVHD) resemble those of several autoimmune diseases, as evidenced by frequent dermal, hepatic, occular, oral, pulmonary, gastrointestinal and neuromuscular involvement. Serosal involvement, however, has only rarely been reported and most of the existing accounts are historical. We describe a boy transplanted in third CR of CALLA-positive ALL from his HLA-identical sister who developed cGVHD, which was complicated by a huge pericardial effusion as a part of severe polyserositis including pleural effusion, ascites, and polyarthritis. The patient shared the HLA antigens HLA-A2, B51, and DQW6 which are associated with autoimmune diseases.

Invasive fungal infections in lymphoma patients receiving immunotherapy following autologous bone marrow transplantation (ABMT).

Invasive fungal infections are quite rare (1-5%) following conventional ABMT for malignant lymphoma. Two high-risk lymphoma patients (one non-Hodgkin's lymphoma (NHL) and one Hodgkin's disease) underwent ABMT followed by immunotherapy as part of an experimental therapy given to 12 lymphoma patients aiming to prevent relapse following transplantation. The post-immunotherapy course in both patients was complicated by invasive fungal infections (pulmonary mucormycosis and generalized aspergillosis). The association between invasive fungal infection and immunotherapy following ABMT for malignant lymphoma patients is discussed.

CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation.

Hemorrhagic cystitis (HC) is a known complication of stem cell transplantation. In contrast to early-onset HC that is usually attributed to cyclophosphamide and occurs within a few days of infusion, late onset HC is associated with viral infection. In recent years BK virus has emerged as an important causative agent. We describe two patients who developed late onset HC (38 and 92 days post transplant) associated with BK viruria concomitant with CMV reactivation and suggest a possible role of CMV in the process of BK virus DNA replication.

Oral tuberculosis following autologous bone marrow transplantation for Hodgkin's disease with interleukin-2 and alpha-interferon immunotherapy.

A patient with Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Six months later while receiving interleukin (IL)-2 and alpha-interferon immunotherapy, he developed a painful lesion in his oral cavity with a fistula in the buccal area. Excision biopsy disclosed necrotizing granulomatous inflammation with acid-fast bacillus. The patient received a 9-month course of isoniazide, rifampin and pyrazinamide, and recovered. The possible pathophysiological mechanism is discussed.

Soluble IL-6 receptors (sIL-6R) in hematological patients receiving immunotherapy with IL-2/IFN-alpha or donor lymphocytes following bone marrow transplantation.

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin-6 (IL-6) which may display antitumor activity. Therefore, we evaluated sIL-6R levels in the sera of 15 patients who received cytokine-mediated immunotherapy with (IL-2/IFN-alpha), and 15 patients who received cell-mediated immunotherapy post-BMT, in an attempt to reduce the relapse rate. sIL-6R levels were evaluated pre-, during and post-cytokine or cell-mediated immunotherapy, using IL-6R-specific monoclonal antibodies (McAb) and double-sandwich ELISA. In normal controls, sIL-6R levels were found to be 20 +/- 3 ng/ml. sIL-6R levels increased significantly during IL-2/IFN-alpha immunotherapy in comparison to pre- or post-immunotherapy levels (74 +/- 9 ng/ml vs 46 +/- 6 ng/ml, and 50 +/- 9 ng/ml, respectively) (n = 15) (P < 0.05). sIL-6R levels also significantly increased following donor lymphokine activated killer (LAK) cells, given in addition to IL-2, in comparison to base line levels (87 +/- 3 ng/ml vs 60 +/- 2 ng/ml) (n = 6) (P < 0.05). Increased levels of sIL-6R were observed in BMT patients treated with immunotherapy.

Multilineage hematopoietic engraftment after allogeneic peripheral blood stem cell transplantation without conditioning in SCID patients.

Successful stem cell transplantation for patients with severe combined immunodeficiency (SCID) from matched family donors without conditioning results in engraftment of T lymphocytes. B lymphocytes engraft in only 50% of the cases, while myelopoiesis and erythropoiesis remain of host origin. Full hematopoietic engraftment was reported in one case after bone marrow transplantation without conditioning for a SCID patient. We studied three SCID patients who were transplanted with unmodified mobilized peripheral blood from HLA-identical family sex-mismatched members. They received megadoses of stem cells (18-23 x 10(6)CD34/kg). In contrast to the expected mixed chimerism that usually occurs in the absence of conditioning, we found in our patients 100% donor cell engraftment based on fluorescence in situ hybridization (FISH) and microsatellite techniques. Subset analysis of the engrafted cells using a multiparametric system enabling a combined analysis of morphology, immunophenotyping and FISH showed that both T and B lymphocytes and myeloid cells were of donor origin in two patients, while T lymphocytes and myeloid cells were of donor origin in the third. In the two cases with ABO incompatibility, erythroid engraftment was evidenced by blood group conversion from recipient to donor type. Multilineage donor engraftment is possible in SCID patients even without conditioning.

Tetraploid myeloid cells in donors of peripheral blood stem cells treated with rhG-CSF.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is frequently used to mobilize CD34+ cells in healthy donors and patient with malignant diseases prior to peripheral blood stem cell (PBSC) harvest. To analyze the effects of rhG-CSF on morphology and genotype of white blood cells, a novel multiparametric cell scanning system that combines morphologic, immune and genotypic analyses of the same cells was used. We report here that tetraploid myeloid cells are present in the peripheral blood of donors treated with rhG-CSF. The tetraploidy was detected in up to 0.6% of differentiated myeloid cells and all observed CD34+ cells were diploid. Thus, short treatment with rhG-CSF of PBSC donors induces numerfical chromosomal alterations in a small subset of mature myeloid cells.