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Mycoses are diseases caused by fungi that involve different parts of the body and can generate dangerous treatment complications. This study aims to analyze fungal infection epidemiology in intensive care units (Pediatric and Cardiac Surgery Intensive Care Units—PCICU) and the Neonatal Intensive Care Unit (NICU) in one large pediatric center in the period 2015–2020 compared with 2005. The year 2005 was randomly selected as a historical time reference to notice possible changes. In 2005 and 2015–2020, 23,334 mycological tests were performed in intensive care units. A total of 4628 tests (19.8%) were performed in the intensive care units. Microbiological diagnostics involved mycological and serological testing. Of the 458 children hospitalized in the NICU, positive results in the mycological tests in the studied years were found in 21–27% of the children and out of 1056 PCICU patients, positive results were noticed in 18–29%. In both departments, the main detected pathogen was Candida albicans which is comparable with data published in other centers. Our experience indicates that blood cultures as well as the detection of antifungal antibodies do not add important information to mycological diagnostics. For the years of observation, only a few positive results were detected, even in patients with invasive fungal diseases. To our knowledge, this is one of a few similar studies over recent years and it provides contemporary reports of mycoses in pediatric ICU patients.

The human microbiota, which consists of trillions of microorganisms, impacts the host’s health and treatment of potential diseases. The role of the microbiota in the development and treatment of childhood leukemia is still not clear. This study reviews the current scientific understanding of the changes in gut microbiota composition during chemotherapy in acute lymphoblastic leukemia (ALL) in children and assesses its impact on the treatment process. The findings show alterations in gut microbiota are obvious at the time of diagnosis of ALL. During intensive chemotherapy, dysbiosis persists, and after treatment, the microbiota restores its diversity. However, there are significant gaps in understanding the impact of gut microbiota on the severity of treatment complications and overall survival rate.

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.

Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). Methods: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983–1993, n = 187), AML-PPGLBC 94 (1994–1997, n = 74), AML-PPGLBC 98 (1998–2004, n = 151), AML-BFM 2004 Interim (2004–2015, n = 356), and AML-BFM 2012 (2015–2019, n = 131). Results: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05, event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05, and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10, 11)(p12, q23) and DEK-NUP214/t(6, 9)(p23, q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD. Conclusions: The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years.

Infections in immunocompromised patients after hematopoietic stem cell transplantation can have a severe and atypical course. Some opportunistic pathogens are difficult to detect in microbiological tests, and that is why treatment success depends on an accurate clinical diagnosis. This article presents a case of a 7-year-old girl with severe aplastic anemia treated with bone marrow transplantation with post-transplantation period complicated by persistent, hectic fever, with peak episodes of 39-40°C, lasting several weeks. Repeated microbiological tests failed to reveal the etiological agent, and empirical anti-infective treatment was ineffective. In the fourth week of fever, imaging showed multiple foci resembling abscesses in the patient's internal organs and, subsequently, in soft tissues. The characteristics of these changes and data concerning environmental exposure led to the clinical diagnosis of cat scratch disease (bartonellosis) with multi-organ involvement and enabled the targeted treatment to be implemented. Fever subsided and organ lesions regressed. In this case, repeated ultrasound imaging was the basic diagnostic tool that helped arrive at a correct diagnosis and implement effective treatment of this life-threatening complication after hematopoietic stem cell transplantation.

Chronic granulomatous disease (CGD) is phagocytic cell metabolic disorder resulting in recurrent infections and granuloma formation. This paper reports the favourable outcome of allogeneic transplantation in six high-risk CGD patients. The following donors were used: HLA-matched, related (two) and unrelated (three), and HLA-mismatched, unrelated (one). One patient was transplanted twice using the same sibling donor because of graft rejection at 6 months after reduced-intensity conditioning transplant (fludarabine and melphalan). Myeloablative conditioning regimen consisted of busulphan and cyclophosphamide. Stem cell source was unmanipulated bone marrow containing: 5.2 (2.6-6.5) × 10(8) nucleated cells, 3.8 (2.0-8.0) × 10(6) CD34+ cells and 45 (27-64) × 10(6) CD3+ cells per kilogramme. Graft-versus-host disease prophylaxis consisted of cyclosporine A and, for unrelated donors, short course of methotrexate and anti-T-lymphocyte globulin. Mean neutrophile and platelet engraftments were observed at day 22 (20-23) and day 20 (16-29), respectively. Pre-existing infections and inflammatory granulomas resolved. With the follow-up of 4-35 months (mean, 20 months), all patients are alive and well with full donor chimerism and normalized superoxide production.

OS is a variant of SCID characterized by generalized erythroderma, alopecia, eosinophilia, and elevated IgE levels. It is fatal unless treated with allogeneic HSCT, which is the only curative approach. However, treatment related complications and graft rejection are major obstacles to the success of treatment. In this report, we describe a patient with OS, complicated by prolonged cytomegalovirus infection, successfully treated by reduced intensity conditioning allogeneic HSCT from sibling donor.

Background: The Wiskott-Aldrich syndrome (WAS) including X-linked thrombocytopenia (XLT) is a complex disorder with a wide range of disease severity and unique hematological and immunological manifestations. Based on this complexity, several approaches are available to these patients, including observation, symptomatic treatment, splenectomy, gene therapy (GT), or allogeneic hematopoietic stem cell transplantation (HSCT). In many instances more than one of these therapeutic options may seem appropriate for any given patient. A prospective, randomized study comparing the pros and cons of these therapeutic options in WAS/XLT would be desirable, but is not feasible due to the rarity and variable severity of the disease, as well as the need for long-term follow-up. Methods and Definitions: We retrospectively assessed via an international, anonymized, file-based survey the consequences of different therapies based on the severity of the disease phenotype and how these therapies affected patients' quality of life as perceived by their treating physician. The frequency of disease- and therapy-related complications with respect to the specific treatment was recorded. "Severe events" were defined as: all fatal events or sepsis, meningitis, pneumonia requiring respiratory support, systemic viral/fungal infections or serious bleeding episodes (intracranial and gastrointestinal) requiring transfusion support. Allogeneic HSCT, splenectomy and GT were defined as "procedures", HSCT and GT as "definitive". Results: A total of 575 patients with a documented WAS gene mutation from 51 centers in 27 countries with a median follow-up of 7.4 years (range: 0.2-75.6), resulting in 5632 patient years, were included in the study. Of these, 240 (42%) carried missense, 67 (12%) nonsense, 90 (16%) splice-site mutations, 77 (13%) deletions, 40 (7%) insertions and 61 (11%) had incomplete or inconclusive mutation information. An allogeneic HSCT was performed in 252 (44%), splenectomy in 78 (14%), GT in 14 (2%) patients, while 264 (46%) patients never had a procedure. At the time of last follow-up or before the first procedure the WAS disease severity score was 1 in 55 (10%), 2 in 144 (25%), 3 in 161 (28%), 4 in 109 (19%) and 5 in 86 (15%) patients. Overall survival of the entire cohort (censored at the time of first definitive procedure, thereby representing the "natural" disease outcome) was 82% (95% confidence interval 78-87) at 15 years and 70% (61-80) at 30 years of age. Ten year overall survival after HSCT was 80 % (74-85). The cumulative incidence (CI) of severe bleeding, severe infection, autoimmunity or malignancy in patients without a procedure at last follow-up or censored before the first procedure was 45% (39-50), 61% (55-66), 46% (40-52) and 31% (25-37) respectively at 15 years of age and 61% (51-69), 70% (62-76), 62% (52-70) and 45% (35-53) at 30 years. The frequency of definitive procedures (HSCT or GT) increased in patients with higher WAS scores, while better natural disease outcomes were associated with lower WAS scores. Overall quality of life (QoL) as perceived by the treating physician was very good, good, limited or unacceptable in 85/457 (19%), 172/457 (38%), 176/457 (39%) and 24/457 (5%) of patients without or before a procedure respectively. QoL was also strongly correlated with the WAS score. At last follow-up after successful HSCT QoL improved to very good in 123/184 (67%), good in 47/184 (26%), limited in 12/184 (7%) and unacceptable in 2/184 (1%). Splenectomy also had a favorable effect on QoL with 16/52 (31%) very good, 24/52 (46%) good, 9/52 (17%) limited and 3/52 (6%) unacceptable. Platelet counts improved from a baseline mean of 36G/l to 91G/l after GT, 159G/l after splenectomy and 204G/l after HSCT. Conclusion: This study presents outcome data of the largest cohort of patients with a WAS gene mutation studied so far and confirms the anticipated spectrum of disease severity and the curative effect of HSCT. The data show that untreated patients with WAS suffer from increasing rates of disease-associated complications over time which correlates well with a significant reduction of QoL. Both HSCT and splenectomy have a positive effect on physician-perceived QoL. Due to the large cohort size this study's data will allow us to assess the influence of specific genotypes on outcome in WAS (analysis ongoing), possibly allowing for more individualized treatment recommendations in the future. Disclosures Albert: GSK: Research Funding.

Currently, granulocyte colony stimulating factor (G-CSF) alone or in combination with myelosuppresive chemotherapy remain the standards of CD34+ cells mobilization allows the safe and successful collection of adequate peripheral blood stem cells (PBSC) for autologous transplantation. However, in up to 30% of patients mobilization of PBSC is ineffective. This report presents our experience in mobilization and collection of peripheral blood stem cells in 82 children with different proliferative disease. In mobilization G-CSF was administered alone in steady state (56 patients, pts) or in combination with myelosuppresive chemotherapy (26 pts). The CD34+ cell count at least 10 cells/ml was required to start apheresis procedure, which was repeated, if needed, during following 1-4 days until collection of at least 2 (optimally 3) x106 CD34+ cells/kg b.w. of recipient was obtained. Three pts in each group (3/ 56 and 3/26) failed the first course of mobilization. The median number of CD34+ cells mobilized was 4.8 (0.5-15) x106/kg b.w. The minimal and optimal number of CD34+ cells for transplantation was achieved in 85% and 61% of patients in the G-CSF + chemotherapy group and in 84% and 54% in the G-CSF group, respectively. The efficacy of presented mobilization arms in our group was similar. However, the incidence of infection and total hospitalization time during mobilization were higher in chemotherapy + G-CSF group.

The aim of the study was the evaluation of safety and efficacy of vaccination in children after stem cell transplantation.21 patients, 1.4-22 (average 7.8) years old, 13 boys and 8 girls after autologous (11-52%) and allogeneic (10-48%) transplantation were included in the vaccination protocol. Indications for transplantation were: neoplastic disease--16, immunodeficiencies--3 and aplastic anaemia 2 cases. Time between transplantation and beginning of vaccination protocol was 0.8-4 (average 1.5) years. Vaccination protocol was constructed on the basis of the European Group for Blood and Marrow Transplantation indications. We have evaluated: (1) quality of recipient immune reconstitution and protection against common pathogens (2) immunogenicity of revaccination schedule; (3) safety of the vaccination programme.With the exception of one patient presenting with repeated fever, lymph node enlargement, muscle and joint pain, no important side effects were observed. Meningococcial meningitis developed in one patient who refused vaccination. The mean concentrations of antibodies in the plasma before and after vaccination were as follows: anti-diphteria (54; 2285), anti-tetanus (136; 3149) and anti-hepatitis B virus (anti-HBs: 24; 474) IU/ml.(1) Vaccination in patients after transplantation is efficient and well tolerated. (2) Significant increase of antibody level was detected. (3) Any delay in beginning the vaccination can result in life threatening complications.

In departments of neurology, neurosurgery and hospice care there is a group of patients with compete motor function impairment having normal central nervous system function. Victims of spinal cord injury, cerebral palsy, cerebral stroke, loss of extremities, neuromuscular diseases, between others belong to them. Since two decades an intensive studies of use of brain waves to steer peripheral equipments has been performed. Brain Computer Interface and Brain-Machine Interface will allow in the near future for even partial restore of skills in permanently disabled patients. Recently new sets composed of games steered by brain waves have been introduced to the market. Exercises with such equipment will help to control an ability to concentrate and precise steer of the peripheral electronic equipments. The next phase will be use of the new skills to steer the wheelchairs and other computer programs with the brain signals to control own healthy organs or artificial machines.

Congenital and acquired neurodegradative diseases are always the reason for prolonged stay in hospital, at the beginning of the establishment of diagnosis and treatment and afterwards for stabilizing all functional adaptation to an existence with the severe disability. Also infections of the lower respiratory tract accompanying the later course of the disease are usually directed to hospital treatment. The aim of the study was to delineate the role of hospice care of patients staying at home, in economical approach to the medical care of severly and incurably ill children. The study group consisted of 29 children with neurodegradative diseases, aged 6 months to 18 years, admitted to the home care of Priest Józef Tischner Cracovian Children' Hospice. The costs of yearly treatment (based on 2008 data) of the infections of the lower airways in the studied group, performed at home under the hospice care and in hospital, were compared. The actual expenses of home treatment were counted. Considering the hospital therapy costs, the simulation was performed following median expenses of a 10-day-treatment of a 20 kg-in-weight child with uncomplicated lower respiratory tract infection in pediatric department with the use of the first line therapy antibiotic. Three parameters were taken to calculations: the medical care costs, the expenses of laboratory tests and X-ray pictures and the costs of antibiotics. In studied children 61 cases of lower respiratory tract infections were diagnosed in 2008 (the median incidence was 2,1 per year; ranged 0-7), of which 48 cases were treated at home. The median time of antibiotics administration in home treatment was 13 days. In 31% of infections more than one antibiotic was used. In 19% of cases in home therapy parenteral medicine was necessary. The median summarized cost of treat- ment at home was calculated as 2657 zl. The need for hospital care in our group concerned 13 incidences. The median estimated cost of treatment of the lower airways infection in hospital for one child equaled 4942 zl. The expenses of home treatment of the lower airways infections under the hospice care were twice lower than the costs of the therapy in hospital. Apart from the obvious psychological and social benefits, also economic aspect contributes to the promotion of the hospice care of staying-at-home patient in the improvement of medical care for children with severe neurodegradative diseases.

Infections are one of the most important clinical problem and most frequent cause of interventions among chronically ill children under hospice care. Frequent and long-lasting hospitalizations before admission to the hospice cause patients' colonization with nosocomial pathogens. These pathogens usually cause returning infections, difficult to cure in home care. The aim of the study was evaluation of colonization by multidrug-resistant organisms and infections' frequency in chronically and incurably ill children under care of the Cracow Children's Hospice of Father J. Tischner. We analyzed infections in patients of the Hospice in 2008-2009. Frequency of infections, their localization, pathogens and necessity of hospitalization were evaluated. On the basis of microbiological examination we distinguished infections caused by multidrug resistant pathogens. Ninety microbiological examination were made in 24 children. Urine, stool, pharyngeal and nasal swap and others were examined. Nosocomial pathogens including Gram-negative rods with ESBL phenotype, Gram-positive Enterococci with HLAR phenotype and Staphylococci with MRCNS and MRSA phenotype were isolated in 36 (40%) examinations, in 17 (71%) patients. Frequency of infections was higher in patients colonized by nosocomial pathogens in comparison with patients without colonization, but difference was not statistically important. There are many factors that increase risk of infections and make them difficult to treat, like: immobilization, impaired swallowing and coughing reflexes, thorax deformation, neurogenic bladder, tracheostomy. Multi-drug resistant pathogens are additional risk factor that can lead to the necessity of hospitalization. In chronically and incurably ill patients time of hospitalization should be minimized to reduce the risk of colonization with multi-drug resistant pathogens.

Hemophagocytic syndrome (HS) is a rare but life-threatening disease caused by inappropriate activation of T-lymphocytes and histiocytes, hipercytokinemia and hemophagocytosis. The most common symptoms are fever, hepatosplenomegaly, unspecific neurological abnormalities, pancytopenia, coagulopathy, hiperferritinemia and lipid abnormalities. HS is classified into two forms: primary, inherited (Familial Hamophagocytic Lymphohistiocytosis--FHL) and secondary (associated with infection, malignancy, autoimmune disease). In spite of the fact that diagnostic guidelines are available it often remains unrecognised. Prognosis of HS depends on the form of disease and in case of secondary HS on the underlying disease. Development of the treatment protocols (HLH-94, HLH-2004) which combine immunochemiotherapy with hematopoietic stem cell transplantation has strongly improved prognosis in HS especially in the primary form. Three-year overall survival for children with HS is now over 50%. Early diagnosis and appropriate therapy is crucial for effectiveness of the treatment. Popularisation of the knowledge about the syndrome, diagnostic guidelines and treatment protocols can contribute to more frequent appropriate recognition of HS and to improvement of the treatment results.

The aim of the study was to evaluate the efficacy of hepatitis B prophylaxis in children with acute lymphoblastic leukemia (ALL) and to try to determine the optimal procedure of protection against the infection. The retrospective analysis included 229 patients with ALL divided into three groups depending on the type of anti-HBV prophylaxis. The group 1 (1990-91, 38 patients) received only sporadically passive prophylaxis, in the group 2 (1992-94, 55 patients) passive prophylaxis was regular, and the patients of the group 3 (1995-2001, 138 children) received complete active and passive prophylaxis. Among vaccinated children three subgroups were additionally distinguished: subgroup a--vaccination was completed before the disease, subgroup b--the cycle of vaccination began before and continued during the therapy, subgroup c--the whole cycle of vaccination was performed during the ALL treatment. The efficacy of the prophylaxis was evaluated taking into account the incidence of hepatitis B and the level of anti-HBs antibodies in vaccinated children. Additionally the incidence of hepatitis C was assessed to evaluate the role of unspecific prophylaxis. The incidence of hepatitis B in the group 1, 2, and 3 was: 57.9%, 23.6%, and 0.76%, respectively, and the incidence of hepatitis C: 44.7%, 36.4%, and 5.9%, respectively. The percent of the failure of active prophylaxis in the subgroup a, b, and c was: 29%, 53%, and 93%, respectively. In spite of the reduction of exposure to the infection (unspecific prophylaxis), the role of specific prophylaxis is essential. The program of passive and active prophylaxis used by us is efficient in preventing hepatitis B in children with ALL. However, during the intensive chemotherapy only passive prophylaxis should be used with postponement of the vaccination because of very low response to the vaccination applied in this phase of treatment. Regular control of anti-HBs antibodies' level is essential in all patients with leukemia even in those with initially high level of antibodies.

Hereditary hemochromatosis (HH) is characterized by excess iron deposition. Two mutations in the HFE gene are associated with HH. Heterozygous carriers of HFE mutations are at higher risk of developing type 2 diabetes mellitus (T2DM). The aims of our project were to identify the frequency of C282Y and H63D mutations in a population from the Małopolska region of south-eastern Poland, and to search for an association of HFE mutations with T2DM.We included 391 individuals in this study: 222 T2DM patients and 169 controls. Genotypes were determined by electrophoresis of the DNA digestion products from SnaBI and DpnII, respectively. Differences in distributions between the groups were then analyzed by the chi-squared test.The frequency of wild/C282Y alleles was 98.2%/1.8% in T2DM patients and 96.7%/3.2% in controls (p=0.19). The frequency of wild/H63D alleles was 85.6%/14.4% and 88.8%/11.2% (p= 0.19), respectively. The distribution of genotypes was not statistically different. However, in stratified analyses based on age of T2DM onset and gender, we observed a higher prevalence of wild/H63D and H63D/H63D genotypes among T2DM patients diagnosed at49 years of age, the mean age for the entire group (p=0.018), and among male T2DM individuals (p=0.005) than in controls.The frequency of HH-associated mutations in this population from south-eastern Poland is similar to other Caucasians. We found no evidence for the association of the C282Y mutation with T2DM. The results do suggest, however, that the H63D mutation may play a role in the pathogenesis of late onset T2DM and in males in this Polish population.

Multiple Myeloma (MM) is the second most commonly diagnosed hematologic malignancy and still an incurable disease with dismal prognosis and average survival of 3 – 4 years. None of conventional therapies gives total cure or long survival, so it is urgently necessary to find new treatment strategies. Heat shock protein 90 (HSP90) is a potentially good therapeutic target, because it interacts with diverse and wide panel of client proteins that are important for proliferation and survival of tumor cells. Geldanamycin (GA) and its analog 17-allylaminogeldamycin (17AAG) are HSP90 inhibitors and were shown to block various tumor cells growth including MM cells. 17AAG has been already tested in clinical trials and showed some antitumor properties. There are, however, other inhibitors belonging to geldanamycin family such as: 17DMAG, 17DMAP and 17AEP which have not been tested against multiple myeloma cell lines and primary samples. In this study we looked at the influence of GA and its analogs on proliferation and apoptosis of MM cells. We found that GA at 100 nM concentration inhibited growth of MM cells by 80%, 17AEP by 75%, 17DMAG and 17DMAP by 70% and 17AAG by 30%. Primary MM cells were more resistant and at 100 nM concentration we observed 30% inhibition with GA and 17DMAG. At the same time 17AAG did not effectively inhibit proliferation of primary MM cells. We also analyzed influence of 100 nM concentration of GA and analogs on the apoptosis of MM primary cells and cell lines after 6 h and 24 h of incubation. Percentage of Anexin V and propidium iodine double positive geldanamycines treated primary MM cells was similar to the control after 6 h but change after 24 h. In comparison to control, number of apoptotic cells increased by: 175% for 17DMAG, 140% for GA, 80% for 17DMAP and 17AEP, no changes in number of apoptotic cells were observed for 17AAG. Similar observation was made for MM cell lines and increase in number of Anexin V positive cells was noticed. Again, percentage of Anexin V positive cells did not increase after treatment with 17AAG and remained at the control level. We also observed, similarly to others, substantial block in G1 and G2/M phase of cell cycle in cells treated with GA and its analogs. In conclusion, besides to 17AAG other HSP90 inhibitors could be considered as potential therapeutics for treatment of MM. Particularly, based on our data, we suggest that 17DMAG and 17AEP are new HSP90 inhibitors that should be tested in a clinic because they exert strong MM cells growth inhibition.

Despite progress in the treatment of Multiple Myeloma (MM), it is still an incurable disease with average survival of 3–4 years. Because MM is often resistant to conventional therapies, new treatment strategies are necessary. The presence of elevated HGF (Hepatocytic Grow Factor) expression has been well documented in multiple myeloma. The c-met oncogene has been shown to be present in MM cell lines at the mRNA and protein level. Some data suggested that this axis could be responsible for proliferation and inhibition of apoptosis in MM cells. In this study we have analyzed c-met expression in 15 patients with (MM) before and after treatment. Seven of these pts responded well and eight pts responded poorly to the employed therapy. All 15 pts were c-met positive before therapy. Bone marrow cellularity of patients who responded well was 76% before (range: 10% – 100%) and 46% after treatment (range: 40% – 60%). In this group plasmocyte infiltration of bone marrow consisted of 59% before (range: 10% – 80%) and 9% after chemotherapy (range: 0% – 20%). Five of them had undetectable c-met positive cells among bone marrow cells after treatment. In the group of poor responders cellularity of bone marrow was 40% (range: 20% – 70%) before treatment and 46% (range: 20% – 70%) after therapy. Plasmocytes consisted of 20% (range: 10% – 50%) of bone marrow cells before and 44% (range: 10% – 90%) after treatment. All patients in this group had cells positive for c-met receptor after therapeutic regiment. This results suggested that c-met-HGF axis might be a good target for alternative therapy in MM. We looked for potential therapeutics that interferes with this axis and we found that geldanamycin (GA) has been shown to decrease expression of c-met at the protein level in several different cell types. Using inhibitors that belongs to geldanamycin family (GA, 17AAG and 17DMAG) we treated MM cell lines and primary sample. We found that these molecules strongly inhibited expression of c-met in both MM cell lines and patients sample as assessed by western blot analysis. We also tested the influence of these inhibitors on proliferation of MM cells. We found that 100nM dose of GA and 17DMAG inhibited growth of MM cell lines by 80% and 100nM dose of 17AAG inhibited growth of these cells by 20%. Primary cells were more resistant to treatment but we still obtained 30% inhibition with GA and 17DMAG. 17AAG was ineffective and proliferation decreased by less than 10%. Grow inhibition was probably not only due to c-met-HGF axis blockade because these molecules also inhibit other proteins (AKT, RAF). In our experiments we have shown that the level of c-met expression correlates with response to therapy. Patients who respond well had substantially decreased number of c-met positive plasmocytes after chemotherapy in comparison to poor responders. We have also showed that drugs that block c-met-HGF axis could be used in treatment of MM. These drugs could potentially inhibit cells proliferation, increase apoptosis and disrupt MM cells interaction with bone marrow environment. Based on these data we postulate that the c-met receptor is a potential target for MM therapy especially in patients who do not respond to the first line of treatment.