Blood stream infections during chemotherapy-induced neutropenia in adult patients with acute myeloid leukemia: treatment cycle matters.

The purpose of this study was to assess the frequency of blood stream infections (BSIs) during neutropenia in different cycles of intensive chemotherapy treatment in acute myeloid leukemia (AML). The register data of 327 consecutive patients aged 16-66 years having de novo AML between September 1992 and December 2001 were prospectively gathered in five Finnish tertiary care leukemia centers. The patients had not received fluoroquinolone prophylaxis. Reported BSI rates were compared during neutropenia in four chemotherapy treatment cycles (C). There were 956 treatment episodes, with 456 (47.7%) positive blood cultures. BSI was monomicrobial in 327 episodes (71.7%) and polymicrobial in 129 (28.3%). The overall incidence rate (per 1,000 hospital days) for BSI was 13.2, varying from 6.8 in CI after idarubicin, conventional-dose cytarabine, and thioguanine to 15.6 in CII, 15.8 in CIII, and 17.6 in CIV. The distribution of monomicrobial gram-positive BSIs was as follows: CI, 71.7%; CII, 62.8%; CIII, 53.3%; CIV, 36.6%; and CI-IV together, 43.2%. The most common finding in the four different cycles was coagulase-negative staphylococci (38.3 to 30.6%). Viridans group streptococci were most commonly observed (in 20.4% of positive blood cultures) during CII after high-dose cytarabine and idarubicin treatments. The distribution of monomicrobial gram-negative BSIs was as follows: CI, 21.7%; CII, 36.3%; CIII, 45.7%; CIV, 46.9%; and CI-IV together, 37.9%. A great variation of incidence and types of microorganisms between AML chemotherapy cycles was found. It would be more reasonable to analyze chemotherapy cycle-based BSI results rather than the overall results.

Blood stem cell mobilization and collection in patients with chronic lymphocytic leukaemia: a nationwide analysis.

Some reports suggest that blood stem cell mobilization is difficult in a proportion of patients with CLL. We evaluated this issue in a large cohort of CLL patients. One hundred and twenty-eight patients with CLL underwent blood stem cell mobilization during 1995-2005 in Finland. Ninety-five percent of the patients had received fludarabine. The most common mobilization regimen was intermediate-dose CY plus G-CSF (90 patients, 70%). At least 2 x 10(6)/kg CD34+ cells were collected after the first mobilization attempt in 83 patients (65%), whereas 45 patients (35%) failed to reach this collection target. No differences were observed between these patient groups with regard to age, time from the diagnosis to mobilization, number of previous treatment lines, number of fludarabine courses, time from the last fludarabine-containing chemotherapy to mobilization, disease status or degree of marrow infiltration. Patients who failed collection had platelets <100 x 10(9)/l more commonly at the time of mobilization (30 vs 4%, P<0.001). A significant proportion of patients with CLL were difficult to mobilize. Adequate marrow function including platelet counts >100 x 10(9)/l seem to be important factors in terms of successful blood stem cell collection.

HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia.

Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to ß2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.

Autologous stem cell transplantation in patients with chronic lymphocytic leukaemia: the Finnish experience.

Although autologous stem cell transplantation (ASCT) has gained some popularity as a treatment option in patients with chronic lymphocytic leukaemia (CLL), limited multicentre data are available on the feasibility and efficacy of this approach. Between January 1995 and June 2005, 72 patients with CLL received ASCT in five Finnish centres. There were 45 men and 27 women with a median age of 57 years (38-69). The median time from diagnosis to ASCT was 32 months (6-181) and the median number of prior regimens 1 (1-4). All patients received blood stem cell grafts and CD34+ selection had been performed in 44 patients (61%). The most common high-dose regimen was a total body irradiation plus cyclophosphamide (38 patients, 53%). No early treatment-related deaths were observed. With a median follow-up of 28 months from ASCT, a relapse or progression has been observed in 27 patients (37%). The projected progression-free survival is 48 months (confidence interval (CI) 30-66). The projected median overall survival is 95 months (CI 74-101) from ASCT and is not influenced by graft selection or conditioning regimen used. Autologous stem cell transplantation is a feasible treatment option for CLL. Randomized trials against alternative treatments are needed to assess the impact of ASCT on the clinical course of CLL.

Autologous stem cell transplantation in elderly (>60 years) patients with non-Hodgkin's lymphoma: a nation-wide analysis.

Limited experience is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in elderly patients with non-Hodgkin's lymphoma (NHL). In 1994-2004 altogether 88 NHL patients > 60 years old received ASCT in six Finnish transplant centres. There were 57 male and 31 female patients with a median age of 63 years (range 60-70 years); 17 patients were>65 years. The histology included diffuse large B cell (n = 29), mantle cell (n = 27), follicular (n = 15), peripheral T cell (n = 12) and other (n = 5). Disease status at ASCT was I complete remission/partial remission (CR/PR) in 53 patients, II CR/PR in 30 patients and other in five patients. The conditioning regimens included BEAC (n = 49), BEAM (n = 34), TBI-CY (n = 4) and other (n = 1). Eighty-four patients received PB grafts. The medians to reach neutrophils > 0.5 and platelets > 20 were 10 and 14 days, respectively. The early treatment-related mortality (TRM) (<100 days) was 11%. With a median follow-up of 21 months for all patients, 45 patients (51%) are alive. A relapse or progression after ASCT has been observed in 32 patients (36%). ASCT is feasible in selected elderly patients with NHL, but the early TRM seems to be higher than in younger patients.

A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma.

The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34+ cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m2 +G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of ⩾3 × 10(6)/kg CD34+ cells with 1-2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P=0.084). The median number of aphereses needed to reach the yield of ⩾3 × 10(6)/kg was lower in arm A than in arm B (1 vs. 2, P=0.035). Two patients needed plerixafor in arm A and five patients in arm B (P=0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.

Telomerase activity in vivo in human malignant hematopoietic cells.

In somatic cells, each DNA replication round gives a shortening of the telomere ends as a consequence of incomplete lagging strand synthesis. Telomeres are essential for chromosomal integrity and extensive telomere length reduction is associated with increased instability of the genome. In germ line cells and in established cell lines, telomerase activity maintains the length of the telomeres by de novo synthesis of telomeric repeats, in humans (T2AG3)n. Recently, it was for the first time shown the existence of telomerase activity in human ovarian carcinomas. In the present study we show that telomerase activation can also occur in human hematopoietic tumor cells in vivo. Cell extracts from 19 cases with leukemia, lymphoma and myeloma were tested for telomerase activity using an in vitro assay with (T2AG3)3 or permutations of this sequence as primers. Eight cases demonstrated an RNAse A sensitive ability to add new nucleotides to the human telomere sequence. Nine acute leukemias were tested telomerase negative. Our data demonstrate that telomerase activation in vivo seems to be a common event in B cell neoplasias with a mature immunophenotype like non-Hodgkin's lymphoma and myeloma, in contrast to acute leukemias of B, T or myeloid cell origin. Telomere length evaluation indicated no marked differences between samples with or without telomerase activity which could argue for a telomere length independent mechanism for telomerase activation in at least some cases.

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group.

In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.

Thalidomide therapy and polyneuropathy in myeloma patients.

Thalidomide is today an increasingly used therapy in advanced and refractory myeloma patients, especially in patients relapsing after high dose therapy. One important and well-known side effect of thalidomide is polyneuropathy (PNP). The purpose of this study was to investigate 1) how severe the thalidomide-induced PNP is in patients treated for myeloma 2) which neurophysiological tests and parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how neuropathic symptoms correlate with neurophysiological changes. Twelve patients received thalidomide for treatment of relapsed multiple myeloma for at least 5 months. Prior to the thalidomide treatment, all patients had been treated with chemotherapy including vincristine, and seven patients had also received cisplatin. PNP symptoms, clinical findings and neurophysiological tests before and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients had minimal and one patient slight PNP. After thalidomide treatment, 4 patients had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons were affected to some extent. Thermal thresholds were not altered, indicating that thin myelinated and unmyelinated axons are spared. The most sensitive parameter for detecting thalidomide-induced PNP was the sensory nerve compound action potential amplitude. The neuropathic symptoms deteriorated significantly during the therapy, but clinically, no patient developed a disabling PNP that would have required interrupting the therapy. The neuropathic side effects of thalidomide seem to be acceptable in myeloma patients.

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for those receiving conventional cytotoxic drugs only. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should be considered for all physically fit patients.

Serum dehydroepiandrosterone sulfate concentration as an indicator of adrenocortical suppression in asthmatic children treated with inhaled steroids.

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 microg/d during the first 2 months and 400 microg/d thereafter. The respective fluticasone propionate doses were 500 and 200 microg/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13-29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8-25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4-16%; P < 0.01) and 6% (95% confidence interval, 16% decrease-3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14-28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0-16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.

Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids.

The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate. Seventy-five asthmatic children were randomly divided into three treatment groups: 30 to the fluticasone propionate (FP), 30 to the budesonide (BUD), and 15 to the cromone (CROM) group. FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter. The respective BUD doses were 800 and 400 microg/day. A low dose ACTH (0.5 microg/1.73 m2) test was performed before treatment and 2, 4, and 6 months later. The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean (<330 nmol/L). The low dose ACTH test was abnormal after both the high and low steroid doses in 23% of the children. At the 4 month measurement there were more abnormal tests in the BUD (n = 9) than in the FP (n = 5) group (P < 0.05). At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group (P < 0.01), whereas the difference between the FP and CROM groups was not significant. During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD, 0.03 in the children treated with FP, and 0.09 in the children treated with CROM; the difference between the BUD and FP groups was significant (P < 0.05). In conclusion, the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids. A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day.

Hypothalamic-pituitary axis remains intact after interferon-alpha treatment in hematologic diseases.

Many endocrinologic disturbances have been reported during and after interferon-alpha (IFN-alpha) treatment. These disturbances have often been caused by autoantibodies. The aim of this prospective study was to evaluate whether IFN-alpha causes hormonal changes and if it is necessary to search for such disturbances routinely. Ten patients with hematologic malignancies were examined before and after 4 months of IFN-alpha treatment. Pituitary function was tested by hypothalamic releasing hormones (thyrotropin-releasing hormone, TRH, growth hormone-releasing hormone, GHRH, gonadotropin-releasing hormone, GnRH). The adrenal glands were tested with the adrenocorticotropin (ACTH) test. The human chorionic gonadotropin (hCG) test was performed on the men (n = 4). The IFN treatment was well tolerated, and no long-term hormonal side effects were found. The testosterone/sex hormone binding globulin (SHBG) index tended to improve. There were no significant differences between the hormone responses before and after IFN-alpha treatment. We conclude that the hypothalamic-pituitary axis remains intact after IFN-alpha treatment. There is no need to follow patients endocrinologically if the patients are not predisposed by autoantibodies.

Technetium-99m-HMPAO-labeled leukocytes and technetium-99m-labeled human polyclonal immunoglobulin G in diagnosis of focal purulent disease.

To evaluate the usefulness of 99mTc-HMPAO-labeled leukocytes and 99mTc-labeled polyclonal human immunoglobulin G (Technescan HIG) in the diagnosis of focal purulent disease, 31 comparative scintigraphies were done in 30 patients with known or strongly suspected focal infection. Focal purulent disease was the final diagnosis in 19 patients. Technetium-99m-labeled leukocytes showed 16 true-positive, no false-positive, 11 true-negative and 3 false-negative findings. The corresponding figures for 99mTc-labeled HIG were 11, 2, 9 and 8. The sensitivity and specificity of imaging with labeled leukocytes were 84% and 100%, respectively, and with labeled HIG, 58% and 82%, respectively. The overall accuracy of the leukocyte scan was significantly better than that of the HIG scan (90% versus 67%, p < 0.001). Thus, if focal infection is suspected, scintigraphy with 99mTc-labeled leukocytes is the preferable method. No cases exhibited a better imaging result with 99mTc-HIG scintigraphy than with 99mTc-labeled leukocytes.

Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine.

Forty patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) preceded by MDS were treated with intensive induction and consolidation chemotherapy in a prospective multicenter pilot study. They were given two cycles of cytarabine 100 mg/m with 12-h intervals on days 1-7 and idarubicin 12 mg/m2 on days 5-7, both intravenously. Patients who were in remission after these two cycles were given two further cycles of cytarabine on days 1-5 and idarubicin on day 5. No maintenance treatment was given. Eleven out of 19 MDS patients (58%) and 10 out of 21 AML patients (48%), in total 21 out of 40 patients (53%), entered remission. Eight patients underwent allogeneic bone marrow transplantation. The follow-up time was 13-48 (median 33) months. At the time of the analysis, seven patients survived, four patients with MDS all of whom had been treated with bone marrow transplantation (three in continuous remission), and three patients with AML treated with chemotherapy only (two in continuous remission). The median survival of the patients treated with chemotherapy only was 12 months, with the median progression-free survival being 8 months. In view of the poor prognostic factors of the patients, the remission rate was satisfactory, but the responses as well as the survival were short. The post-remission treatment needs to be improved.

Autologous blood cell transplantation in B-CLL: response to chemotherapy prior to mobilization predicts the stem cell yield.

Successful stem cell mobilization and collection is possible in B-CLL after a favorable response to preceding chemotherapy, and also after treatment with the new nucleoside analogues fludarabine and cladribine. A poor response, on the other hand, seemed to predict a mobilization failure. CD34+ cell selection resulted in a 2- to 3-log reduction of the CLL cells in the harvests. Engraftment with both unselected and selected progenitor cells was rapid, and need for hospitalization was short. High-dose therapy with stem cell rescue appears to be capable of inducing CRs of high quality, but so far the follow-up is too short to define whether this will be translated into prolonged disease-free survival.

Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults.

To evaluate the late-effects of allogeneic bone marrow transplantation (BMT) on endocrine function 20 adults (10 females, 10 males) with hematological malignancies were studied after a mean of 3.2 years (range 1.0-10.0) following BMT. The mean age of patients at the time of BMT was 39 years. Dynamic tests of the hypothalamic-pituitary axis included growth hormone releasing hormone (GHRH), gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) stimulations with measurements of serum growth hormone (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and prolactin (PRL) responses. Adrenal function was assessed with the adrenocorticotropin (ACTH) test. Five patients (25%) had a subnormal GH response to GHRH stimulation, but all had a normal serum insulin-like growth factor I (IGF-I) value. There was an inverse nonlinear relationship between the body mass index (BMI; kg/m2) and GH response but no relation between the GH response and total body irradiation (TBI), intrathecal treatment or occurrence of graft-versus-host disease. In females, serum FSH and LH basal levels and responses to GnRH, in spite of oestrogen substitution therapy in 9/10 patients, indicated ovarian failure and early menopause. Most responses to GnRH were delayed. All males had elevated serum basal FSH levels indicating damage in seminiferous tubulus and infertility. Serum basal LH was elevated only in four males but testosterone values were all within normal limits. However, the mean free androgen index (FAI) was in the low normal range, and two subjects had abnormally low FAI. Serum free thyroxine (fT4) levels were normal in all but one, but an exaggerated TSH response to TRH occurred in seven patients (35%). Four of them had received TBI and one total nodal irradiation suggesting radiation-induced damage to the thyroid gland. In 19 of the 20 patients, adrenal function judged with ACTH test was normal. We conclude that functional impairments of the hypothalamus-pituitary-gonad/thyroid axis are common while disturbances in GH, adrenal and prolactin occur less often in patients after intensive treatment and BMT. Typically, the target organ is more commonly affected than the hypothalamus-pituitary axis. In spite of normal serum testosterone and LH values, serum FAI may reveal androgen deficiency.

Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma.

We describe a patient with multiple myeloma who was treated with intensive therapy and autologous blood cell transplantation as her first-line treatment. The disease relapsed 3 months after the transplant as plasma cell leukemia and the patient succumbed in 4 weeks. We suggest that an aggressive plasma cell clone may be selected during the course of intensive treatment. Complex karyotypic findings are also presented.

Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma.

Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD+/-local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m(2)) (n=25) or intermediate-dose CY (ID-CY, 4 g/m(2)) (n=32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 x 10(6)/kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, P<0.001), lower frequency of fever (20 vs 73%, P<0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P=0.004) and days on parenteral antibiotics (0 vs 4 days, P<0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile.

Bone mineral density after allogeneic bone marrow transplantation.

Bone turnover markers and bone mineral density (BMD) were studied in 25 adult patients (14 females, 11 males) who had undergone allogeneic bone marrow transplantation (BMT). The interval from BMT to the first examination was at least 1 year (mean 3, range 1-10). Mean age of the patients at the time of first evaluation was 42 (range 19-54) years. Blood samples and urine collections for evaluation of biochemical factors reflecting skeletal turnover were performed together with the first BMD measurement. BMD was measured from the lumbar vertebrae (L2 to L4) with computed tomography and results were expressed as Z-scores. At the time of the first measurement five patients (20%) had Z-scores <-2.5 s.d. and 12 patients (48%) between -1 and -2.5 s.d. In 12 patients BMD assessments were repeated and it seemed that reduction in BMD had mostly occurred during and shortly after BMT and remained the same during follow-up. The cross-linked carboxyterminal telopeptide of type I collagen (ICTP) correlated negatively with BMD (r = -0.45, P = 0.045) as did bone-specific alkaline phosphatase (BAP; r = -0.64, P = 0.002). No correlation between BMD and time interval from diagnosis to BMT, conditioning regimen, corticosteroid use or hospital stay during transplantation was found. In conclusion, bone disease is common after BMT. Our findings demonstrate an increased collagen and bone turnover and a high risk of osteoporosis. BMD measurements must be repeated regularly and collagen markers such as ICTP and BAP can be beneficial in estimating the activity of bone disease.