Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria.

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab).

Background: The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods: Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results: At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion: Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number: NCT01724021 (ClinicalTrials.gov).

The prevalence of small intestinal bacterial overgrowth and methane production in patients with myelomeningocele and constipation.

STUDY DESIGN: Prospective study. OBJECTIVES: The objective of this study was to assess the prevalence of small intestinal bacterial overgrowth (SIBO), methane (CH4) production and orocecal transit time (OCTT) in children affected by myelomeningocele. SETTING: This study was conducted at the Catholic University in Rome, Italy. METHODS: Eighteen (6M/12F; 16.4±7.6 years) children affected by myelomeningocele were enrolled. All subjects underwent H2/CH4 lactulose breath tests to assess SIBO and OCTT. All patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. A nephro-urological clinical evaluation of the number of urinary tract infections (UTIs) and neurogenic bowel disease score were also performed. RESULTS: Thirty-nine percent (7/18) of the children showed SIBO and 61% (11/18) presented a delayed OCTT. Moreover 44.4% (8/18) produced high levels of CH4. Interestingly, all myelomeningocele children who produced CH4 showed a delayed OCTT and a higher incidence of UTI, with a lower frequency of evacuation, compared with those with a normal or accelerated OCTT. CONCLUSION: The association between CH4 and constipation suggests that CH4 has an active role in the development of constipation. One of the most interesting features of our study is to identify a correlation between myelomeningocele, CH4, delayed OCTT and UTI. The intestinal decontamination with locally acting drugs in these children may reduce the number of UTIs and improve intestinal motility.

Endoscopic pancreatic sphincterotomy in patients with IPMN-related recurrent pancreatitis: A single center experience.

BACKGROUND: Acute recurrent pancreatitis (ARP) is a rare manifestation of Intraductal Papillary Mucinous Neoplasms (IPMN) of the pancreas; ARP is a relative indication for pancreatic surgery in the setting of IPMN. Endoscopic pancreatic sphincterotomy (EPS) has been described as a minimal invasive treatment to reduce the episodes of ARP secondary to mucus migration in IPMN. METHODS: patients with IPMN-related ARP treated with ESP from January 2004 to December 2020 were retrospectively selected. Clinical and technical data were recorded. A clinical follow-up (minimum 12 months) was performed to assess the number of episodes of AP occurring after EPS. RESULTS: 25 patients were included. The mean follow-up after ESP was 93.4 months (SD± 56.6). The mean number of AP before and after EPS were respectively 3.29 (SD ± 1.04) and 0.51 (SD ± 0.71). A complete response (no further episodes of AP) and a partial response (>50% reduction of AP episodes) were obtained in 64% and 24% of the cases, respectively, with an overall response rate of 88%. One post-EPS bleeding and one minor-papilla stenosis were reported and were endoscopically managed. Two patients underwent pancreatic resection for the occurrence of high-risk stigmata for cancer progression. CONCLUSIONS: EPS is a safe and effective treatment to reduce the number of episodes of AP in selected patients with IPMNs-related ARP. Prospective trials are needed to confirm these data.

The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

A prospective survey of febrile events in hematological malignancies.

The Hema e-Chart prospectively collected data on febrile events (FEs) in hematological malignancy patients (HMs). The aim of the study was to assess the number, causes and outcome of HM-related FEs. Data were collected in a computerized registry that systematically approached the study and the evolution of FEs developing in a cohort of adult HMs who were admitted to 19 hematology departments in Italy from March 2007 to December 2008. A total of 869 FEs in 3,197 patients with newly diagnosed HMs were recorded. Fever of unidentified origin (FUO) was observed in 386 cases (44.4%). The other causes of FE were identified as noninfectious in 48 cases (5.5%) and infectious in 435 cases (50.1%). Bacteria were the most common cause of infectious FEs (301 cases), followed by fungi (95 cases), and viruses (7 cases). Mixed agents were isolated in 32 episodes. The attributable mortality rate was 6.7% (58 FEs). No deaths were observed in viral infection or in the noninfectious groups, while 25 deaths were due to FUO, 16 to bacterial infections, 14 to fungal infections, and three to mixed infections. The Hema e-Chart provided a complete system for the epidemiological study of infectious complications in HMs.

Folate in gastrointestinal health and disease.

OBJECTIVE: Folate has heterogeneous functions and is involved in several activities in both animal and human body. It is an important constituent of our organism, and its bioavailability is mainly dependent from the correct function of our gastrointestinal tract. Our aim is to describe what happens to folate homeostasis in gastrointestinal health and disease, analyzing the alterations of folate metabolism in some specific conditions of intestinal and liver impairment. DISCUSSION: Folate absorption and metabolization involve the small intestine and the liver; in conditions of gastrointestinal tract disease (i.e. celiac disease, liver disease) folate function may be compromised with important consequences on the whole organism. Moreover, folate deficiency may produce gastrointestinal alterations too. For this reason, the gastrointestinal tract could be the responsible but also the victim of folate deficiency. CONCLUSIONS: The presence of folate deficiency should always be assessed in patients with a gastrointestinal disease. Further studies are needed to assess the role of folates in gastrointestinal tract diseases and in other gynecologic, neurologic, psychiatric, cardiovascular, ophthalmic and neoplastic diseases. Folates supplementation could be considered, in the future, as an effective complimentary therapy in several pathologic conditions.

The impact of the multidisciplinary tumor board (MDTB) on the management of pancreatic diseases in a tertiary referral center.

BACKGROUND: The implementation of multidisciplinary tumor board (MDTB) meetings significantly ameliorated the management of oncological diseases. However, few evidences are currently present on their impact on pancreatic cancer (PC) management. The aim of this study was to evaluate the impact of the MDTB on PC diagnosis, resectability and tumor response to oncological treatment compared with indications before discussion. PATIENTS AND METHODS: All patients with a suspected or proven diagnosis of PC presented at the MDTB from 2017 to 2019 were included in the study. Changes of diagnosis, resectability and tumor response to oncological/radiation treatment between pre- and post-MDTB discussion were analyzed. RESULTS: A total of 438 cases were included in the study: 249 (56.8%) were presented as new diagnoses, 148 (33.8%) for resectability assessment and 41 (9.4%) for tumor response evaluation to oncological treatment. MDTB discussion led to a change in diagnosis in 54/249 cases (21.7%), with a consequent treatment strategy variation in 36 cases (14.5%). Change in resectability was documented in 44/148 cases (29.7%), with the highest discrepancy for borderline lesions. The treatment strategy was thus modified in 27 patients (18.2%). The MDTB brought a modification in the tumor response assessment in 6/41 cases (14.6%), with a consequent protocol modification in four (9.8%) cases. CONCLUSIONS: MDTB discussion significantly impacts on PC management, especially in high-volume centers, with consistent variations in terms of diagnosis, resectability and tumor response assessment compared with indications before discussion.

Congenital glioblastoma.

We describe the case a 2-day-old female with congenital glioblastoma. Total resection was followed by adjuvant and high dose chemotherapy, as indicated by the current Italian infant protocol. The child is alive and well 18 months after diagnosis. A review of 67 selected congenital brain tumors showed the mortality rate was 82%. Even though the majority of patients had glioblastoma, only 5/67 had received adjuvant therapy. To ensure optimal outcomes, we recommend total or subtotal surgical resection, followed by adjuvant and high dose chemotherapy. Given the lack specific protocols for congenital brain tumors an international consensus seems to be needed, starting with congenital glioblastoma.

Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States.

Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft. Haploidentical transplant modalities are based mainly on high-intensity conditioning regimen, but reduced intensity regimens have recently been introduced. The graft may be a megadose of extensively T cell-depleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of GVHD- and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling. Improvements will come with successful implementation of strategies to accelerate and strengthen post transplant immune reconstitution as well as transplantation of patients in early stage disease.

Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.

BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

Competing risk analysis using R: an easy guide for clinicians.

In the last decade with widespread use of quantitative analyses in medical research, close co-operation between statisticians and physicians has become essential from the experimental design through all phases of complex statistical analysis. On the other hand, easy-to-use statistical packages allow clinicians to perform basic statistical analyses themselves. Since the software they most commonly use does not perform in depth competing risk analysis, we recommend an add-on package for the R statistical software. We provide all the instructions for downloading it from internet and illustrate how to use it for analysis of a sample dataset of patients who underwent haematopoietic stem cell transplantation for acute leukaemia.

Alternative donor transplants for adult acute lymphoblastic leukaemia: a comparison of the three major options.

Myeloablative sibling-matched allogeneic transplantation for adult acute lymphoblastic leukaemia provides the best outcome, but most patients lack a suitable, related histocompatible donor. We reviewed three haematopoietic stem cell donor sources used for alternative donor transplantation pointing out drawbacks of these approaches including inherent selection bias. Matched unrelated donor allografts most often are performed in Philadelphia chromosome-positive disease and in second complete remission (CR2); a nearly 30% event-free survival (EFS) can be anticipated in select patients. Transplants using haploidentical donors are most successful if undertaken in CR1 and CR2 and appear to produce EFS rates of about 25%. Limited umbilical cord blood transplant data suggest efficacy, but marked patient and treatment heterogeneity hamper conclusions. Each of these three strategies has unique potential benefits and disadvantages. The growing use of minimal residual disease detection may identify subgroups of patients unlikely to be cured by chemotherapy alone; these patients are candidates for upfront high-dose chemoradiotherapy and cellular immunotherapy. These three approaches are plagued by treatment-related mortality and relapse rates as high as 40%, but advances in technology and supportive care may make each stem cell source more feasible and efficacious.

Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.

The relationship between bone marrow (BM) cytokine and chemokine levels, cytogenetic profiles and skeletal involvement in multiple myeloma (MM) patients is not yet defined. This study investigated a cohort of 455 patients including monoclonal gammopathy of uncertain significance (MGUS), smoldering MM and symptomatic MM patients. Skeletal surveys, positron emission tomography (PET)/computerized tomography (CT) and magnetic resonance imaging (MRI) were used to identify myeloma bone disease. Significantly higher median BM levels of both C-C motif Ligand (CCL)3 and CCL20 were found in MM patients with radiographic evidence of osteolytic lesions as compared with those without, and in all MM patients with positive PET/CT scans. BM levels of CCL3, CCL20, Activin-A and Dickkopf-1 (DKK-1) were significantly higher in patients with high bone disease as compared with patients with low bone disease. Moreover, CCL20 BM levels were significant predictors of osteolysis on X-rays by multivariate logistic analysis. On the other hand, DKK-1 levels were related to the presence of MRI lesions independently of the osteolysis at the X-rays. Our data define the relationship between bone disease and the BM cytokine and chemokine patterns highlighting the tight relationship between CCL20 BM levels and osteolysis in MM.

PML is required for telomere stability in non-neoplastic human cells.

Telomeres interact with numerous proteins, including components of the shelterin complex, whose alteration, similarly to proliferation-induced telomere shortening, initiates cellular senescence. In tumors, telomere length is maintained by Telomerase activity or by the Alternative Lengthening of Telomeres mechanism, whose hallmark is the telomeric localization of the promyelocytic leukemia (PML) protein. Whether PML contributes to telomeres maintenance in normal cells is unknown. We show that in normal human fibroblasts the PML protein associates with few telomeres, preferentially when they are damaged. Proliferation-induced telomere attrition or their damage due to alteration of the shelterin complex enhances the telomeric localization of PML, which is increased in human T-lymphocytes derived from patients genetically deficient in telomerase. In normal fibroblasts, PML depletion induces telomere damage, nuclear and chromosomal abnormalities, and senescence. Expression of the leukemia protein PML/RARα in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone marrow of pre-leukemic mice. Our work provides a novel view of the physiologic function of PML, which participates in telomeres surveillance in normal cells. Our data further imply that a diminished PML function may contribute to cell senescence, genomic instability, and tumorigenesis.

Galectin-1 suppression delineates a new strategy to inhibit myeloma-induced angiogenesis and tumoral growth in vivo.

Galectin-1 (Gal-1) is involved in tumoral angiogenesis, hypoxia and metastases. Actually the Gal-1 expression profile in multiple myeloma (MM) patients and its pathophysiological role in MM-induced angiogenesis and tumoral growth are unknown. In this study, we found that Gal-1 expression by MM cells was upregulated in hypoxic conditions and that stable knockdown of hypoxia inducible factor-1α significantly downregulated its expression. Therefore, we performed Gal-1 inhibition using lentivirus transfection of shRNA anti-Gal-1 in human myeloma cell lines (HMCLs), and showed that its suppression modified transcriptional profiles in both hypoxic and normoxic conditions. Interestingly, Gal-1 inhibition in MM cells downregulated proangiogenic genes, including MMP9 and CCL2, and upregulated the antiangiogenic ones SEMA3A and CXCL10. Consistently, Gal-1 suppression in MM cells significantly decreased their proangiogenic properties in vitro. This was confirmed in vivo, in two different mouse models injected with HMCLs transfected with anti-Gal-1 shRNA or the control vector. Gal-1 suppression in both models significantly reduced tumor burden and microvascular density as compared with the control mice. Moreover, Gal-1 suppression induced smaller lytic lesions on X-ray in the intratibial model. Overall, our data indicate that Gal-1 is a new potential therapeutic target in MM blocking angiogenesis.

Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia.

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell-depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell-depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

Peripheral blood progenitor cell mobilization in healthy donors receiving recombinant human granulocyte colony-stimulating factor.

OBJECTIVE: We analyzed the incidence of primitive (LTC-IC) and committed (CFU-mix, BFU-E, CFU-GM) hematopoietic progenitors detected under steady-state conditions and upon progenitor cell mobilization in a cohort of healthy donors receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF). MATERIALS AND METHODS: Healthy donors (n = 30) of HLA-mismatched or -matched stem cell transplants were mobilized with rhG-CSF (8 microg/Kg body weight subcutaneously twice daily until completion of leukapheresis). PBPC collections were started after 4 days of rhG-CSF therapy. RESULTS: Steady-state incidence of bone marrow LTC-IC, but not committed progenitors, significantly correlated with the numbers of mobilized CD34+ cells (r = 0.6, p = 0.004), CFU-GM (r = 0.79, p = 0.0005) and CFC (r = 0.76, p = 0.001) detected after 4 days of rhG-CSF therapy. Statistically significant correlations were also found between steady-state blood CFU-GM and peak numbers of CD341 cells (r = 0.68, p = 0.001), numbers of day 4 CD341 cells (r = 0.52, p = 0.005), CFU-GM (r = 0.63, p = 0.002), and CFC (r = 0.61, p = 0.003). CONCLUSION: Our data show that in normal volunteers baseline marrow LTC-IC and blood CFU-GM correlate with rhG-CSF-mobilized PBPC. The potential clinical relevance of these findings in the identification of poor mobilizers will be tested in a prospective study.