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ObjectivesPsychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre–post-program changes in psychosocial wellbeing.MethodThe research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months–5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program.ResultsThirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion.Significance of resultsThe MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.

There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) scanning in primary mediastinal B-cell lymphoma (PMBL). We analyzed 28 patients with PMBL treated with chemotherapy, of whom 25 (89%) also received rituximab and 17 (61%) radiotherapy. PET-CT scans were interpreted using visual analysis and a 5-point scale. After a median follow-up of 2.6 years, four patients relapsed and two died. The 2-year progression-free survival and overall survival were 86% and 94%. PET-CT has excellent negative predictive value (interim, 86-87%; end of treatment, 95%) but limited positive predictive value due to the high frequency of positive scans. Several patients with persistent metabolically active masses underwent biopsies, which showed necrosis but no lymphoma. Thus a negative PET-CT is an excellent predictor of subsequent outcome. However, residual metabolically active masses after treatment should be biopsied to confirm viable lymphoma prior to salvage therapy.

The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12 study patients (SP; lymphoma n=10 or myeloma n=2) with pegfilgrastim (6 mg SC stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were 'predicted poor-mobilizers' and six were 'predicted adequate-mobilizers'. Peripheral blood (PB) CD34(+) monitoring commenced on D3. Apheresis commenced on D4. Comparison was with 22 historical controls (HC; lymphoma n=18, myeloma n=4; poor mobilizers n=4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34(+) count ⩽5 × 10(6)/L D3 post pegfilgrastim; all SP surpassed this threshold the morning after plerixafor. In SP, PBCD34(+) counts peaked D4 6/12 (50%), remaining ⩾5 × 10(6)/L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers (⩾2 × 10(6)/kg) within four aphereses. After maximum four aphereses, median total CD34+ yield was higher in SP than HC; 8.0 (range 2.4-12.9) vs 4.8 (0.4-14.0) × 10(6)/kg (P=0.04). Seven of twelve (58%) SP achieved target yield after one apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (n=2), diarrhoea (n=2) and facial paraesthesiae (n=3). Plerixafor+pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers, and is superior to pegfilgrastim alone.

The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3-101) months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62-86 %) and 88 % (75-94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology; in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.

Haematopoietic stem and progenitor cells (HSPC) mobilization, using cytokine-alone, is a well-tolerated regimen with predictable mobilization kinetics. Single-dose pegfilgrastim mobilizes HSPC efficiently; however, there is surprisingly little comparative data on its use without chemotherapy for HSPC mobilization. Pegfilgrastim-alone and filgrastim-alone mobilization regimens were compared in 52 patients with haematological malignancy. Pegfilgrastim 12 mg (n=20) or 6 mg (n=2) was administered Day 1 (D1) in 22 patients (lymphoma n=17; myeloma n=5). Thirty historical controls (lymphoma n=18; myeloma n=12) received filgrastim 10 mcg/kg daily from D1. Peripheral blood (PB) CD34(+) counts reached threshold (5 × 10(6)/L) and apheresis commenced on D4(4-5) and D4(4-6). Median PB CD34(+) cell count on D1 of apheresis was similar (26.0 × 10(6)/L (2.5-125.0 × 10(6)/L) and 16.2 × 10(6)/L (2.6-50.7 × 10(6)/L); P=0.06), for pegfilgrastim and filgrastim groups, respectively. Target yield (2 × 10(6) per kg CD34(+) cells) was collected in 20/22 (91%) pegfilgrastim patients and 24/30 (80%) in the filgrastim group (P=0.44), in a similar median number of aphereses (3(1-4) versus 3(2-6), respectively; P=0.85). A higher proportion of pegfilgrastim patients tended to yield 4 × 10(6) per kg CD34(+) cells; 16/22 (73%) versus 14/30 (47%) filgrastim patients (P=0.09). One pegfilgrastim patient developed hyperleukocytosis that resolved without incident. Pegfilgrastim-alone is a simple, well-tolerated, and attractive option for outpatient-based HSPC mobilization with similar mobilization kinetics and efficacy to regular filgrastim.

The role of the peripheral blood (PB) CD34(+) cell count in predicting the CD34(+) cell yield in hematopoietic progenitor cell apheresis collections is well established. However, sometimes unexpectedly poor CD34(+) cell yields are obtained. To determine the effect, if any, of a range of factors on the ability of the PB CD34(+) count to predict collection CD34(+) cell count, we performed a retrospective analysis on consecutive hematopoietic progenitor cell apheresis collections between 2004 and 2008. Factors investigated included mobilization regimen, PB white blood cell count, body weight, and disease. After exclusion of collections involving apheresis complications, a total of 1,225 PB CD34(+) cell results with corresponding collection CD34(+) cell results from 458 patients were analyzed. Although differences in the median PB CD34(+) cell counts and collection CD34(+) cell counts were seen between mobilized collections with chemotherapy plus granulocyte colony-stimulating factor and those with granulocyte colony-stimulating factor alone, the predictive capability of the PB CD34(+) cell count for the collection CD34(+) cell yield remained similar. Although poorer collection efficiencies were observed in the myelodysplastic syndrome/myeloproliferative disorder diagnostic subgroup, our findings confirm that PB CD34(+) cell analysis remains a powerful and irreplaceable tool for predicting hematopoietic progenitor cell apheresis CD34(+) cell yield.

This review evaluates the latest information on the mobilisation of haemopoietic stem cells for transplantation, with the focus on what is the current best practice and how new understanding of the bone marrow stem cell niche provides new insights into optimising mobilisation regimens. The review then looks at the mobilisation of mesenchymal stromal cells, immune cells as well as malignant cells and what clinical implications there are.

The mobilization and collection of hematopoietic stem and progenitor cells (HSPC) is central to many potentially curative treatments for cancer and some non-malignant conditions. Recombinant human cytokines have been the mainstay of therapeutic HSPC mobilization, particularly G-CSF. Even with currently used mobilization regimens using G-CSF with or without chemotherapy, up to 60% of patients can fail to mobilize enough HSPC for a transplant procedure. Recombinant human stem cell factor (ancestim, rhSCF, Stemgen) is another such cytokine, which has shown promising synergy when used in combination with G-CSF for HSPC mobilization. It provides a useful second-line option for prior failed-mobilizer patients and those who are anticipated to mobilize poorly due to recognised risk factors. It may also have utility in promoting bone marrow recovery in cases of refractory bone marrow failure such as aplastic anaemia and prolonged non-engraftment after allogeneic HSPC transplantation. We review the literature supporting the use of rhSCF in the context of HSPC mobilization and bone marrow failure. The emergence of other novel agents for HSPC mobilization such as plerixafor (AMD3100, Mozobil) will further demarcate the role of Ancestim as a second- or third-line mobilization agent for the mobilization-refractory patient.

Failure to mobilize adequate numbers of hematopoietic stem and progenitor cells (HSPC) is an important clinical problem. Since bone marrow (BM) neutrophils play a central role in HSPC mobilization, we hypothesized that granulocyte colony-stimulating factor (G-CSF)-mediated mobilization would be enhanced by further expanding the size of the BM granulocyte pool.We tested the potential of the retinoic acid receptor alpha (RARalpha) specific agonist VTP195183, and the pan-RAR agonist all-trans retinoic acid (ATRA), to enhance G-CSF-mediated mobilization of HSPC, in two mouse strains.Pretreatment of mice with VTP195183 significantly increased the number of leukocytes, colony-forming cells, and early engrafting hematopoietic stem cells (HSC) mobilized in the blood in response to G-CSF. In contrast, ATRA had only a marginal effect on G-CSF-induced mobilization. HSPC mobilization synergy between VTP195183 and G-CSF occurred only when mice were preconditioned with VTP195183 prior to G-CSF. This preconditioning was shown to increase the numbers of granulocyte/macrophage progenitors in the BM. Treatment with VTP195183 and G-CSF was accompanied by enhanced levels of active neutrophil proteases in the BM extracellular fluid compared to G-CSF treatment alone.VTP195183 treatment increases the numbers of immature granulocyte progenitors in BM and subsequently synergizes to enhance G-CSF-mediated mobilization of HSPC. These data demonstrate a novel approach to improve G-CSF-induced mobilization by accelerating granulocyte maturation in the BM. These findings are currently being tested in a clinical trial of VTP195183 plus G-CSF for mobilization of HSPC in human patients.

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.

Background: The usefulness of positron emission tomography with computed tomography (PET–CT) in the surveillance of patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission after primary therapy is not well studied. Methods: We performed a retrospective review of our database between 2002 and 2009 for patients with de novo DLBCL who underwent surveillance PET–CT after achieving complete metabolic response (CMR) following primary therapy. Results: Four-hundred and fifty scans were performed in 116 patients, with a median follow-up of 53 (range 8–133) months from completion of therapy. Thirteen patients (11%) relapsed: seven were suspected clinically and six were subclinical (all within first 18 months). The positive predictive value in patients with international prognostic index (IPI)

In a recent edition of this journal, Fianchi et al . [1] retrospectively analyzed the outcomes of 31 patients with chronic myelomonocytic leukemia (CMML) treated with the hypomethylating agent azacitidine. Th ere was variation in the dose schedule of azacitidine, although the majority of patients received 75 mg/m 2 subcutaneously over a 7-day period. After a median number of 6 cycles, the overall response rate was 51%, including 42% of patients achieving complete remission. Th e median overall survival from commencement of azacitidine was 37 months. Analysis of this cohort was signifi cant, given the limited data available on the effi cacy of azacitidine in chronic myelomonocytic leukemia (CMML). Th e large phase III trials describing the effi cacy of azacitidine and decitabine in patients with myelodysplastic syndromes (MDS) included only 35 patients with CMML treated with either agent [2 – 4]. As a result, the generalizability of the results of these trials to patients with CMML is unclear, and therefore retrospective case series provide the best available data to establish the effi cacy of these agents in this setting. To investigate whether our own clinical experience refl ected the fi ndings of Fianchi et al ., we retrospectively reviewed the outcomes of 11 patients with CMML treated with azacitidine at our center between 2008 and 2012. Patients fulfi lling the 2008 World Health Organization (WHO) criteria [5] for diagnosis of CMML and who had received at least one cycle of azacitidine were included. Treatment consisted of azacitidine at a schedule of 75 mg/m 2 subcutaneously daily for 7 days per cycle, with a planned cycle length of 28 days. One patient had a shortened cycle length of 21 days due to highly proliferative disease. Six patients (55%) received concurrent therapy with either thalidomide or lenalidomide within clinical trials [6]. Responses were assessed using the modifi ed International Working Group Criteria (2006) [7]. Patient characteristics are shown in Table I. Seven patients (64%) had CMML-1 and four (36%) had CMML-2. Our cohort included a signifi cant proportion of patients with an elevated baseline white cell count (WCC): four (36%) patients had WCC 13 10 9 /L. Five were red cell transfusion-dependent at baseline. Of the 10 patients who had cytogenetic analysis performed at baseline, two (18%) had poor-risk cytogenetics including abnormalities of chromosome 7. Our patient cohort received a median number of 8 cycles (range 2 – 29) of therapy and had a median follow-up time of 15.9 months (range 2.8 – 38.1months). At the time of analysis, four patients continued to receive treatment with azacitidine. Th e overall response rate was 55% (95% confi dence interval [CI] 28 – 79%). Th is comprised one complete response (CR), three marrow CR, one partial response (PR) and one patient who achieved a hematologic improvement (HI) in erythroid and platelet lineages. Four patients had stable disease and one had progressive disease as their best response. In the patients who attained a disease response, the median time to fi rst response and duration of response were 4.1 months (range 1.6 – 8.2) and 7.0 months (range 2.3 – 13.4), respectively. Response rates appeared similar between patients with CMML-1 or -2 (50% vs. 57%). Th e response rate was numerically higher in patients with a lower white cell count ( 13 10 9 /L) or monocyte count

Poor mobilization of autologous peripheral blood stem cells (HPC-A) in patients requiring high dose chemotherapy represents an ongoing clinical challenge. A key diffi culty in interpreting the literature in this area is that there is no uniform defi nition of poor mobilization. A mobilization “ failure ” at one institution may represent “ suboptimal mobilization ” at another, and thresholds for defi ning a peripheral blood CD34 count as suffi cient to commence collection vary dramatically between institutions. Th e most common reason for a failure to mobilize and collect HPC-A is prior exposure to cytotoxic chemotherapy, in particular protracted courses of alkylators and purine analogs [1 – 3]. More recently lenalidomide exposure has also been implicated in impairment of HPC-A [4]. A recognition and avoidance of these risk factors and the well-timed use of novel mobilization therapies such as plerixafor have seen a lower incidence and greater ability to salvage those patients demonstrating HPC-A mobilization [5,6]. Where repeated attempts at salvage mobilization have been required to obtain a transplantable dose of cells, there are concerns that this subset of hard-to-mobilize patients have an adverse disease-free and overall survival following autologous transplant [7]. Th e mechanism of the suboptimal outcome in patients with a history of poor HPC-A is likely to be complex. Th is group of patients is enriched for patients with refractory disease, who are likely to have residual tumor involvement within the marrow resulting in cell contamination of the graft (the signifi cance of which remains uncertain [8]), and bone marrow microenvironmental damage as a result of multiple lines of prior therapy and multiple mobilization attempts. As a result of these factors and despite the application of granulocyte-colony stimulating factor (G-CSF) and/or plerixafor there is a small group of patients who ultimately cannot achieve an adequate collection for safe autologous transplant. In this edition of Leukemia and Lymphoma , Crocchiolo and co-authors explore whether a history of poor mobilization continues to impart a similar adverse outcome in a cohort of patients with multiple myeloma or lymphoma despite receiving a normal stem cell donation from an allogeneic donor following reduced intensity conditioning [9]. In a retrospective analysis they identifi ed two cohorts of patients who had previously attempted autologous stem cell mobilization but for various reasons proceeded to allogeneic transplant. Compared to the cohort of prior “ good mobilizers, ” defi ned as a CD34 cell count 20 10 9 /L on the fi rst day of apheresis, the group of “ poor mobilizers, ” who failed to achieve this threshold, had an increased non-relapse mortality. Th is diff erence was not due to impaired myeloid engraftment, as post-allogeneic transplant recovery of neutrophils and platelets was similar in the two cohorts. Somewhat paradoxically, assessment of a sub-cohort who, despite being defi ned as poor mobilizers, ultimately succeeded in the collection of 2 10 6 /kg CD34 cells, showed a slower neutrophil engraftment. Th is fi nding may refl ect a group enriched for patients in whom the disease risk resulted in an imperative to move to transplant, which in turn led to more collection days and/or more repeated mobilization attempts, and who were likely to be more heavily pretreated, with a resultant impairment of the bone marrow microenvironment and delayed allogeneic stem cell engraftment. Overall the poor mobilizer cohort had similar rates of relapse and graft-versus-host disease to those of the good mobilizers. Despite this, the non-relapse mortality and overall survival were signifi cantly worse in the poor mobilizer group. Th is fi nding was independent of the patient/donor gender matching or number of prior autografts. No clear pattern emerged in the cause of death in these patients. In the allograft setting, where the engrafting cells are presumably healthy, the putative “ lesion ” in graft dysfunction is likely to be the marrow microenvironment. Whilst platelet and neutrophil engraftment were not clearly impaired in this study, immune reconstitution was not measured. Recovery of lymphocyte subsets, and perhaps just as importantly lymphocyte function, may lag substantially in poor mobilizer patients. Where it has been studied, posttransplant lymphocyte recovery is directly correlated with post-transplant outcome in the autograft and allograft setting [10 – 12]. Impaired lymphocyte recovery in the poor mobilizer group could translate to increased susceptibility

Transplantation with 2-5 × 106 mobilized CD34+cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established. To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify poor mobilizers, and what are the criteria for preemptive and immediate salvage use of plerixafor.

Mantle cell lymphoma (MCL) has aptly been described as a lymphoma with features of ‘the worst of both worlds,’ being both incurable and aggressive, historically with a median survival of 3–5 years ...

It is tempting to assume that faster granulocyterecovery following high dose chemotherapy andautologous stem cell transplant (ASCT) will resultin enhanced patient outcomes of fewer infections,less antibiotic usage, more rapid resolution ofmucositis, and faster discharge from hospital, withall of the cost savings that would naturally followfrom such outcomes.The use of granulocyte colony-stimulating factor(G-CSF) following ASCT does indeed result infaster neutrophil recovery of approximately 2 days inmany reported series, as reviewed by Ojeda et al. [1].However, despite this, studies have been inconsistentin showing that routine use of G-CSF providesadvantages such as reductions in antibiotic use andhospitalization days and improved cost-effectiveness.Acknowledging the obligatory period of neutropeniaprior to the engraftment of granulocytic precursors inASCT, some investigators have studied the use ofdelayed G-CSF administration post-transplant, andhave shown that despite later commencement andless total G-CSF use there was no erosion of clinicaladvantage [2–5]. Despite the variation observed inclinical outcome in these studies there remainssome confusion regarding the value of routine useof G-CSF post-ASCT, a situation reflected in thepositive recommendation for routine G-CSF usepost-ASCT by the American Society of ClinicalOncology (ASCO) guidelines [6], but a lowerrecommendation in the European Society for Med-ical Oncology (ESMO) guidelines [7].In recent years, the availability of a pegylatedpreparation of G-CSF has logically led to theinvestigation of its utility for the support of neutro-phil engraftment following ASCT. In this issue ofLeukemia and Lymphoma, Wanneson and col-leagues report their experiences of post-ASCToutcomes in relatively uniformly treated populationsof patients undergoing ASCT for either myeloma orlymphoma, comparing pateints treated with pegy-lated (Peg)-G-CSF to a matched cohort of patientswho received standard-of-care G-CSF on eitherdayþ5 or dayþ7 [8].Their results indicate that Peg-G-CSF administra-tion did indeed result in more rapid neutrophilrecovery, by approximately 1.5 days, 2 days lessantibiotic use, and a shortening of duration of in-hospital stay by 1 day. The size and retrospectivenature of this cohort analysis precluded performing ameaningful cost–benefit analysis, although it isunlikely that, at current drug costs, an overall costsaving would probably have been observed. Whilstthe clinical improvements were assumed to reflectfaster neutrophil engraftment, it remains possible thatthe improved outcomes were a result of a Peg-G-CSFinduced increase in the pre-nadir neutrophil num-bers, resulting in an overall shorter time with severeneutropenia. Overall, the findings from Wannesonet al. suggest that the biological effect of a single doseof Peg-G-CSF from dayþ1 post-ASCT is similar orslightly enhanced to that delivered by daily G-CSF.This is a finding in line with that observed in otherstudies of Peg-G-CSF administration followingASCT [9,10].One important finding from the Wanneson analysisis that patients undergoing ASCT for differentindications (myeloma vs. lymphoma) may experiencedifferent levels of advantage from post-ASCT G-CSFadministration. Patients with multiple myeloma re-ceiving dayþ1 Peg-G-SCF post-ASCT experienced

Deregulated cell survival programs are a classic hallmark of cancer. We have previously identified a serine residue (Ser585) in the βc subunit of the granulocyte-macrophage colony-stimulating factor receptor that selectively and independently promotes cell survival. We now show that Ser585 phosphorylation is constitutive in 20 (87%) of 23 acute myeloid leukemia (AML) patient samples, indicating that this survival-only pathway is frequently deregulated in leukemia. We performed a global expression screen to identify gene targets of this survival pathway and report a 138-gene βc Ser585-regulated transcriptome. Pathway analysis defines a gene network enriched for PI3-kinase target genes and a cluster of genes involved in cancer and cell survival. We show that one such gene, osteopontin (OPN), is a functionally relevant target of the Ser585-survival pathway as shown by siRNA-mediated knockdown of OPN expression that induces cell death in both AML blasts and CD34+CD38−CD123+ leukemic progenitors. Increased expression of OPN at diagnosis is associated with poor prognosis with multivariate analysis indicating that it is an independent predictor of overall patient survival in normal karyotype AML (n = 60; HR = 2.2; P = .01). These results delineate a novel cytokine-regulated Ser585/PI3-kinase signaling network that is deregulated in AML and identify OPN as a potential prognostic and therapeutic target.

Reported rates of central nervous system (CNS) involvement in mantle cell lymphoma (MCL) are highly variable but substantial (4-26%). Data is lacking regarding risk factors for CNS relapse, and for those patients in whom CNS prophylaxis could be beneficial. We present single institution retrospective analysis of data of baseline features, clinical course, rate of CNS disease and putative risk factors in 62 patients with MCL (18 female, 44 male). CNS disease (all cases were symptomatic) occurred in four patients at a median of 12 months (range 1-58) from diagnosis, with a crude incidence of 6.5% and 5-year actuarial incidence of 5 +/- 3%. Two cases had blastic MCL at diagnosis. Survival after CNS relapse ranged from 2-9 months. Patients who developed CNS disease had a significantly shorter survival from diagnosis than those who did not (P = 0.0024). Symptomatic CNS disease in patients with MCL either at presentation or relapse is an uncommon but devastating complication. In younger patients, more aggressive immuno-chemotherapy regimens containing CNS-penetrating agents may reduce the incidence of CNS disease. While not routinely justified for all patients, CNS prophylaxis may particularly benefit patients with blastic histology at diagnosis, or those with systemic relapse after first-line treatment.

Fludarabine exposure leads to impaired peripheral blood stem cell (PBSC) mobilization in indolent lymphoproliferative disorders (LPD). We previously reported that only 34% of fludarabine-exposed patients mobilized successfully using granulocyte-colony stimulating factor (G-CSF; median 10 microg/kg/day) with or without chemotherapy, with unpredictable kinetics and moderate infectious morbidity. Stem cell factor (SCF) plus high-dose twice daily (b.d.) G-CSF may improve mobilization in these patients. SCF 20 microg/kg/day subcutaneously was given from day 1, G-CSF 12 microg/kg b.d. subcutaneously from day 4, apheresis commenced from day 6. Previous study patients served as historical controls. Thirty five patients with indolent LPD were enrolled, median age was 54 years (range 31-66), 66% male, median cumulative prior fludarabine dose was 660 (405-900) mg. Overall, 22 patients (63%) collected >or= 2.0 x 10(6)/kg PBSC (success), compared to 34% controls (odds ratio (OR) 3.2; 95% confidence interval (CI) (1.2, 9.3); P=0.021). Median CD34(+) yield overall was 2.3 x 10(6)/kg (0.53-8.97) from median four (2-6) aphereses. Study patients >or= 50 years mobilized successfully more frequently than controls (58 versus 17%; P=0.0065). Adjusting for age, successful mobilization remained significantly higher in the current study (OR 4.2; 95% CI (1.4, 14.0); P=0.008). SCF/high-dose b.d. G-CSF improves PBSC mobilization efficacy after fludarabine exposure, over mobilization using G-CSF as the mobilizing cytokine. This combined growth factor strategy is a preferred mobilization method for fludarabine-exposed patients.

Opportunistic infection with invasive aspergillosis (IA) is increasingly frequent in immunocompromised patients, particularly in those with hematological malignancies. In this setting, IA typically involves the lung, with extra-pulmonary involvement usually occurring in the setting of disseminated infection. We report a case of localized gastrointestinal IA complicating induction chemotherapy for acute myeloid leukemia (AML). Oral voriconazole was successful as primary treatment, with no evidence of progressive infection despite further myelosuppressive chemotherapy. A review of the literature suggests that although localized gastrointestinal IA is rare, involvement of the gastrointestinal tract is not uncommon in disseminated infection. Thus, in patients with hematological malignancies who develop significant gastrointestinal symptoms, we recommend that endoscopic investigations and biopsies are performed to exclude IA as a potential cause.

Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graft-versus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n=2) or transformed (n=1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peri-transplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.