Antiemetic prophylaxis in patients undergoing hematopoietic stem cell transplantation: a multicenter survey of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) transplant programs.

A survey within hematopoietic stem cell transplant (HSCT) centers of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) was performed in order to describe current antiemetic prophylaxis in patients undergoing HSCT. The multicenter survey was performed by a questionnaire, covering the main areas on chemotherapy-induced nausea and vomiting (CINV): antiemetic prophylaxis guidelines used, antiemetic prophylaxis in different conditioning regimens, and methods of CINV evaluation. The survey was carried out in November 2016, and it was repeated 6 months after the publication of the Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) specific guidelines on antiemetic prophylaxis in HSCT. The results show a remarkable heterogeneity of prophylaxis among the various centers and a significant difference between the guidelines and the clinical practice. In the main conditioning regimens, the combination of a serotonin3 receptor antagonist (5-HT3-RA) with dexamethasone and neurokin1 receptor antagonist (NK1-RA), as recommended by MASCC/ESMO guidelines, increased from 0 to 15% (before the publication of the guidelines) to 9-30% (after the publication of the guidelines). This study shows a lack of compliance with specific antiemetic guidelines, resulting mainly in under-prophylaxis. Concerted strategies are required to improve the current CINV prophylaxis, to draft shared common guidelines, and to increase the knowledge and the adherence to the current recommendations for CINV prophylaxis in the specific field of HSCT.

Impressive tissue regeneration of severe oral mucositis post stem cell transplantation using cord blood platelet gel.

BACKGROUND: Platelet gel from cord blood (CBPG) is a recently developed blood component for topical use. We report a case of life-threatening mucositis after high-dose chemotherapy with fotemustine and cytarabine that was successfully treated with CBPG. CASE REPORT: A patient with non-Hodgkin lymphoma who was undergoing autologous hematopoietic stem cell transplantation developed severe oral and esophageal mucositis with severe bacterial sepsis and cytomegalovirus infection, causing prolonged neutropenia. CBPG was topically administered daily to the oral cavity. The CBPG was partially reabsorbed and partially swallowed. RESULTS: After 8 consecutive days of administration, the patient's oral mucosa markedly improved, showing restitutio ad integrum, and the patient's clinical status progressively improved. No side effects were seen after CBPG application. CONCLUSION: This case supports the need to conduct controlled studies comparing the efficacy of autologous and allogeneic platelet gel from adult and umbilical cord blood for the topical treatment of severe oral mucositis occurring after high-dose chemotherapy.

A remote lab for experiments with a team of mobile robots.

In this paper, a remote lab for experimenting with a team of mobile robots is presented. Robots are built with the LEGO Mindstorms technology and user-defined control laws can be directly coded in the Matlab programming language and validated on the real system. The lab is versatile enough to be used for both teaching and research purposes. Students can easily go through a number of predefined mobile robotics experiences without having to worry about robot hardware or low-level programming languages. More advanced experiments can also be carried out by uploading custom controllers. The capability to have full control of the vehicles, together with the possibility to define arbitrarily complex environments through the definition of virtual obstacles, makes the proposed facility well suited to quickly test and compare different control laws in a real-world scenario. Moreover, the user can simulate the presence of different types of exteroceptive sensors on board of the robots or a specific communication architecture among the agents, so that decentralized control strategies and motion coordination algorithms can be easily implemented and tested. A number of possible applications and real experiments are presented in order to illustrate the main features of the proposed mobile robotics remote lab.

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study.

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.

Multicenter experience using total lymphoid irradiation and antithymocyte globulin as conditioning for allografting in hematological malignancies.

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects.

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01.

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms.

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo.

Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)-based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m(2)) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)-identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of "new drugs" in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.).

Effect of mental imagery on the development of skilled motor actions.

To test the effect of imagery in the training of skilled movements, an experiment was designed in which athletes learned a new motor action and trained themselves for a month either by overt action or by mental imagery of the action. The experiment was carried out with 30 male karateka (M age = 35 yr., SD = 8.7; M years of practice = 6, SD = 3) instructed to perform an action (Ura-Shuto-Uchi) that they had not previously learned. The athletes were divided into three groups: Untrained (10 subjects who did not perform any training), Action Trained (10 subjects who performed Ura-Shuto-Uchi training daily for 16 minutes), and Mental Imagery (10 subjects who performed mental imagery training of Ura-Shuto-Uchi daily for 16 minutes). The subjects were tested five times, once every 7 days. During each test, they performed a series of 60 motor action trials. In Tests 1, 3, and 5, they also performed a series of 60 mental imagery trials. During the trials, an electroencephalogram (EEG), electromyography (EMG), muscle strength and power, and other physiological parameters were recorded. The results differed by group. Untrained subjects did not show significant effects. In the Action Trained group, training had an effect on reactivity and movement speed, with a reduction of EMG activation and reaction times. Moreover, muscle strength, power, and work increased significantly. The Mental Imagery group showed the same effects on muscle strength, power, and work, but changes in reactivity were not observed. In the Mental Imagery group, the study of Movement Related Brain Macropotentials indicated a progressive modification of the profile of the waves from Test 1 to Test 5 during imagery, showing significant variations of the amplitude of the waves related to the premotor and motor execution periods. Results show that motor imagery can influence muscular abilities such as strength and power and can modify Movement Related Brain Macropotentials, the profile of which potentially could be used to verify the effectiveness of motor imagery training.

Intravascular large B-cell lymphoma associated with silicone breast implant, HLA-DRB1*11:01, and HLA-DQB1*03:01 manifesting as macrophage activation syndrome and with severe neurological symptoms: a case report.

BACKGROUND: Silicone implants have been successfully used for breast augmentation and reconstruction in millions of women worldwide. The reaction to the silicone implant is highly variable; it can lead to local inflammatory symptoms, and sometimes to systemic symptoms and disease. Over 80 cases of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma have been reported in patients with silicone breast implants and have been accepted as a new clinical entity. To the best of our knowledge, an intravascular large B-cell lymphoma associated with a silicone breast implant has not been reported previously. CASE PRESENTATION: A 48-year-old Caucasian woman who presented with high fever was found to have splenomegaly on physical examination. A laboratory diagnosis revealed pancytopenia, hypertriglyceridemia, and hyperferritinemia. She developed signs of altered sensorium, hemiparesis, aphasia, and cauda equina syndrome. On further evaluation, she fulfilled the necessary five out of eight criteria for diagnosis of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Dexamethasone administration was followed by prompt improvement; however, 3 days later she again manifested high fever, which persisted despite administration of immunoglobulin and cyclosporine A. Her silicone breast implant was considered a possible contributor to her macrophage activation syndrome and was therefore removed. A histological examination of the capsule tissue showed an extensive lymphohistiocytic/giant cell foreign body reaction suggestive of autoimmune/inflammatory syndrome induced by adjuvants. However, the histological examination unexpectedly also revealed an intravascular large B-cell lymphoma. CONCLUSIONS: The genetic background of our patient with silicone breast implants might have predisposed her to three rare and difficult to diagnose syndromes/diseases: macrophage activation syndrome/hemophagocytic lymphohistiocytosis, autoimmune/inflammatory syndrome induced by adjuvants, and intravascular large B-cell lymphoma. The simultaneous manifestation of all three syndromes suggests causal interrelationships. Human leukocyte antigen testing in all women who undergo silicon breast implantation could in the future enable us to better evaluate the risk of potential side effects.

Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells.

PURPOSE: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of malignancies characterized by a poor prognosis. We performed a pilot study to investigate the role of reduced-intensity conditioning (RIC) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs. PATIENTS AND METHODS: We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells. The RIC regimen consisted of thiotepa, fludarabine, and cyclophosphamide. The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate. RESULTS: Patients had a median age of 41 years (range, 23 to 60 years). Two patients were primary chemorefractory, and 15 had relapsed disease; eight patients (47%) had a disease relapse after an autologous transplantation. After a median follow-up of 28 months from the day of study entry (range, 3 to 57 months), 14 of 17 patients were alive (12 in complete remission, one in partial remission, and one with stable disease), two died as a result of progressive disease, and one died as a result of sepsis concomitant to acute graft-versus-host disease. The estimated 3-year overall and progression-free survival rates were 81% (95% CI, 62% to 100%) and 64% (95% CI, 39% to 89%), respectively. The estimated probability of nonrelapse mortality at 2 years was 6% (95% CI, 1% to 17%). Donor lymphocyte infusions induced a response in two patients progressing after allografting. CONCLUSION: RIC followed by allogeneic stem-cell transplantation is feasible, has a low treatment-related mortality, and seems to be a promising salvage treatment for relapsed PTCL. These findings suggest that the existence of a graft-versus-T-cell lymphoma effect.

Teicoplanin in patients with acute leukaemia and febrile neutropenia: a special population benefiting from higher dosages.

OBJECTIVE: To define the optimal dosage regimen of teicoplanin that ensures early therapeutically relevant trough concentrations (C(min)) [>10 mg/L at 24 hours and possibly close to 20 mg/L at 48 hours] in patients with acute leukaemia who develop febrile neutropenia after chemotherapy. DESIGN: Prospective observational pharmacokinetic study. PARTICIPANTS: Adult patients (n = 33) with normal renal function previously treated with antineoplastic chemotherapy because of acute lymphocytic or acute nonlymphocytic leukaemia, and subsequently developing febrile neutropenia treated with empirical antimicrobial therapy. DESIGN: First, the standard dosage group (n = 11) was administered standard loading and maintenance doses of teicoplanin (400 mg every 12 hours for three doses followed by 400 mg once daily). Blood samples were collected at defined times as part of routine monitoring and assessed for teicoplanin plasma concentration by fluorescence polarisation immunoassay. Secondly, the high dosage group (n = 22) received a high loading regimen (800 + 400 mg 12 hours apart on day 1, 600 + 400mg 12 hours apart on day 2) followed by a high maintenance regimen (400 mg every 12 hours) from day 3 on. RESULTS: In the standard dosage group, no patient had the recommended teicoplanin C(min) of >or=10 mg/L within the first 72 hours, and only five of the 11 patients (45%) had a C(min) of >or=10 mg/L after 120 hours. No patient had a C(min) of >or=20 mg/L. In the high dosage group, teicoplanin C(min) averaged >or=10 mg/L within 24 hours, and this value was achieved within 48 hours in all but one patient. Of note, C(min) at 72 hours exceeded 20 mg/L in ten of the 22 patients (45%). No patient experienced significant impairment of renal function. CONCLUSIONS: In this patient group, therapeutically relevant C(min) may be achieved very early in the treatment period with loading doses of 12 mg/kg and 6 mg/kg 12 hours apart on day 1, and 9 mg/kg and 6 mg/kg 12 hours apart on day 2, regardless of renal function. Subsequently, in patients with normal renal function a maintenance dosage of 6 mg/kg every 12 hours may be helpful in ensuring C(min) close to 20 mg/L. Assessment of C(min) after 48-72 hours may be useful to individualise teicoplanin therapy. Factors increasing volume of distribution and/or renal clearance of teicoplanin (fluid load, hypoalbuminaemia, leukaemic status) may explain the need for higher dosages.

Survival of elderly patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: The prognosis of elderly patients with acute myelogenous leukemia (AML) is usually dismal, while the true survival of older patients not included in clinical trials is not known. We retrospectively evaluated the impact on survival of an aggressive versus a non-aggressive approach in 1005 patients aged >60 years registered in the database of the GIMEMA cooperative group. DESIGN AND METHODS: Group A patients (n=621) received aggressive treatment, while group B patients (n=384) underwent non-aggressive therapy. The groups were different for risk factor distribution: the patients in group B had a higher median age, worse performance status (PS) and a higher proportion of previous myelodysplastic disease. RESULTS: The overall median survival was 7 and 5 months in groups A and B, respectively (p min of 0.0001). At multivariate analysis the following factors were associated with a significantly shorter survival: age >71 years (RR=1.27; 95% CI=1.07-1.50), PS=2-4 (RR=1.44; 95% CI=1.24-1.68), white cell count > 10,000 mL (RR=1.37; 95% CI=1.06-1.75), and heart dysfunction requiring treatment (RR=1.26; 95% CI=1.05-1.50). No difference in survival was associated with aggressive or non-aggressive treatment (RR=1.1; 95% CI=0.94-1.32). Patients aged min of 70 years, with no heart disease, but a white cell count > 10,000/mL showed a significantly better survival when treated aggressively (median survival 7 vs 3 months, p = 0.011). INTERPRETATION AND CONCLUSIONS: Despite an obvious selection of patients with a worse prognosis in group B, the difference in survival between the two groups was marginal. Multivariate analysis failed to demonstrate a significant survival benefit in aggressively treated patients. All these considerations indicate that elderly patients with AML are overall unlikely to benefit from aggressive treatment, so that this should be offered only to selected patients.

Abnormal cervical cytology after allogeneic bone marrow transplantation.

OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a procedure mostly used for high-risk hematologic malignances. In women, follow-up protocols after BMT include gynecologic checkups with Papanicolaou (Pap) smears. METHODS: We evaluated 117 Pap smears in 54 women who underwent allogeneic BMT and correlated the smear morphology with the BMT-related medical treatment. RESULTS: Abnormal Pap smears after BMT were found in 13 (24.1%) women. Four (7.4%) women had at least one smear with atypical squamous cells of unknown significance, six (11.1%) had a low-grade squamous intraepithelial lesion, and three (5.6%) had atypical squamous cells/high-grade lesion cannot be excluded (ASC-H). The three patients with ASC-H showed high-grade atypia mimicking cancer but had a negative follow-up. Nine women, including the three with ASC-H, had undergone a conditioning therapy for BMT that included busulfan. No association between other drugs and therapy-related atypia was found. CONCLUSIONS: Pap smears after BMT show a high incidence of dysplastic lesions. Moreover, conditioning including busulfan is often associated with therapy-related cytologic atypia, which may lead to unnecessary colposcopies and biopsies. Knowledge of the patient's history and a careful evaluation of the smears are mandatory in these cases.

The impact of histopathologic examination of graft-versus-host disease in the era of reduced-intensity conditioning regimen: a study from the Gruppo Italiano Trapianto di Midollo Osseo.

Reduced-intensity conditioning regimens have reshaped the clinical presentation of graft-versus-host disease after hematopoietic stem cell transplants. However, histopathologic features of graft-versus-host disease following reduced-intensity conditioning regimens have not been fully characterized. In a series of 112 biopsies (skin, n = 60; gastrointestinal [GI] tract, n = 44; liver, n = 8), we described the morphologic profile of graft-versus-host disease following reduced-intensity conditioning and investigated whether histopathologic changes of graft-versus-host disease following reduced-intensity conditioning have a diagnostic and/or prognostic value. Forty-four patients (49.5%) experienced acute graft-versus-host disease, 2 (2.2%) late-onset acute graft-versus-host disease (grade I, n = 13; grade II-IV, n = 33), 24 (27.0%) chronic graft-versus-host disease (de novo n = 12, progressive n = 12) and 19 (21.3%) overlap syndrome. In the skin, we observed: (i) phase-nonspecific changes, such as acute graft-versus-host disease features in chronic graft-versus-host disease patients (n = 4/24; 16.6%), (ii) subtle alterations such as superficial fibrosis in widened dermal papillae (n = 8), in acute graft-versus-host disease/late-onset graft-versus-host disease (n = 6/46; 13.0%) or chronic graft-versus-host disease (n = 2/24, 8.3%) patients, and (iii) features of chronic and acute graft-versus-host disease coexisting in the same specimen in overlap syndrome (n = 3/19; 15.7%). In the GI tract, we did not demonstrate peculiar features differing from those commonly observed in the myeloablative setting. By univariate analysis, a reduced overall survival was associated with graft-versus-host disease type (chronic graft-versus-host disease P = .006, acute graft-versus-host disease P = .03), older age (P = .04), and histopathologic diagnosis of "consistent with" + definite graft-versus-host disease (P = .02). Histopathologic diagnosis retained an independent prognostic value by multivariate analysis (P = .01). The present study indicates that pathologists should be aware of the peculiar morphologic changes of cutaneous graft-versus-host disease following reduced-intensity conditioning and further recommends histopathology in the diagnostic workup of graft-versus-host disease in patients undergoing reduced-intensity conditioning regimen.

Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 x 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B + D vs 48.6% for groups A + C; P = .009), whereas no significant difference was observed between groups A + B and C + D (50.6% vs 56.4%, P = .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients.