S114of a broader randomized controlled trial.It included 44 MM adult patients, who received chemotherapy or biological therapy at Carmel Medical Center in Isreal.Once they sign a consent form, they were randomized into two groups (23 Intervention, 21 Control).In the intervention group, the pharmacist examined the patient's entire medical treatment and sent recommendations to the family physician and hematoocologist.On the day of the treatment, the pharmacist has met with the patient and provided him/her with a discharge counseling in addition to close supervision for 4 months during the treatment period.The control group was treated without increased pharmacological intervention.The data collection phase had ended one month after intervention period.The control group data was examined after the end of treatment to prevent ethical dilemmas.The variables that were examined are compliance, ADR and balancing medical incidences.Results: Intervention group: it was found that 65.2% of the patients did not take their medication according to the manufacturer's instructions, 8.7% took medication that were not registered in their medical fi le, 30.4% took medication at a different dose than recommended, 56% of patients had poor compliance to one or more prophylactic treatments.90 recommendations were sent to the hemato-oncologist -79 (87.7%) were accepted.57 recommendations were sent to the family physicians and 40 (70%) of them were accepted.During the follow-up period, an improvement of 100% in adherence to the manufacturer's instructions, 100% of the medications were registered in the patient's fi le and the response to prophylactic treatment increased to 96%.Among the patients in the intervention group, there was an improvement in the indices of diabetes balance (13%), LDL (34%), vitamin D (30%) and GFR (34%).This is in comparison with an improvement of 4.7%, 9.5%, 23% and a 14% in the control group.During the follow-up period in the intervention group 7 cases of ADR were reported compared to 19 cases in the control group.Conclusion: We found that integrating of a designated pharmacist as part of the hemato-oncology department during the Covid-19 pandemic had high positive effect on the quality and sequence of drug treatment and reduced the incidence of ADR "Crisis is also an opportunity" -integrating a designated pharmacist should be considered even in routine days.

Multiple myeloma is a malignancy of plasma cells, which is highly associated with immune suppression. Consistent with this, reports of outcomes of COVID-19 infection in patients with multiple myeloma show higher rates of severe disease than in the general population.1,2 Protection of this vulnerable patient group from COVID-19 infection is crucial but response to the new vaccines in patients with multiple myeloma is unknown. A recent report showing low anti-SARS-CoV-2 IgG response to the Pfizer vaccine in patients with cancer included 38 patients with haematological malignancies (nine patients with multiple myeloma) and showed only a 13% response rate, raising concerns that multiple myeloma might be associated with attenuated vaccine response.

Abstract Abstract 3125 The median progression free survival (PFS) for younger, fitter patients with multiple myeloma is between 3 and 4 years, however some patients respond very poorly and relapse within a year of autologous transplantation. These patients then go on to receive relapse chemotherapy often with novel agents and, surprisingly, some have a longer remission with second line therapy. The prognostic factors which describe such patients are not well understood, and identifying and treating these patients remains a challenge. To characterise these patients further and describe prognostic markers, we have utilised 2 datasets (1081 patients) comprising 619 patients from the Myeloma IX trial and 462 patients from the Royal Marsden database (RMH). All patients were initially treated with high dose melphalan and peripheral blood stem cell support. Patients were then divided into two groups: early relapse (<12 months from transplant) or late relapse (>12 months after transplant or disease free at last follow up). The Myeloma IX trial consisted of 147 patients (23.7%) in the early relapse group compared to 472 patients (76.3%) in the late relapse group, with a median PFS1 of 7.6 vs. 27.8 months (P<0.001) and OS of 28 vs. 68.8 months (P<0.001), respectively. A similar pattern was seen in the RMH database, where the early relapse group consisted of 86 patients (18.6%) compared to 376 patients (81.4%) in the late relapse group, and with a median PFS of 6.3 vs. 38.6 months (P<0.001) and OS of 31.9 vs. 117.9 months (P<0.001), respectively. In order to describe prognostic factors for early relapse after autologous transplant, we utilized the Myeloma IX dataset, and show that a low Hb, a low platelet count, a low serum albumin, ß2M ≥5.5 mg/L, an ISS Stage III combined with adverse cytogenetics such as t(4;14) and 1q21+ at time of diagnosis predict for an early relapse (<12 months after transplant). In addition, we used Affymetrix gene expression profiling (GEP) to identify significant genes associated with early relapse. A distinct GEP signature containing 38 genes was identified as being associated with early relapse after transplantation, among which 10 genes were on chromosome X. We then used the Royal Marsden dataset to investigate the clinical outcome for patients who relapsed early following second line treatment. To do this, we divided the early relapse group (<12 months from transplant) into two groups: patients with a longer second remission than first remission (47 patients, group A) and patients with a shorter second remission than first remission (39 patients, group B). The median PFS after second line therapy between the two groups was 11.7 vs. 1.8 months (P<0.001) and the median OS was 51.5 vs. 23.0 months (P<0.001), respectively. Univariate analysis showed that a low Hb, a low platelet count, a high ß2M and an ISS stage III at time of second line therapy and no maintenance therapy after second line treatment predicted for a shorter second remission. Failure to achieve a response at the time of first transplant or post second line therapy was highly correlated with a shorter second remission and very aggressive disease outcomes. Multivariate analysis confirmed that failure to achieve a response after second line therapy was the only significant factor correlated with a shorter second remission, and poor survival. Taken together, our data demonstrates that approximately 20% of patients undergoing HDT will have a short remission. High ISS stage, adverse cytogenetics and failure to achieve a response to chemotherapy can be used to identify this group. In addition GEP signature can also identify such patients. About 45% of these early relapse patients will go on to have a very poor outcome, but 55% can be rescued with novel agents. Important aspects to consider in treating these patients are: careful assessment of the bone marrow reserve, the use of a non-cross reacting agent for second line treatment, an early assessment of response to therapy and incorporating novel agent maintenance therapy. Paying attention to these factors will hopefully prolong progression free survival, overall survival and in the end, quality of life in this poor prognosis group. Disclosures: Davies: Celgene, Johnson & Johnson, Onyx, Novartis: Honoraria, Speakers Bureau; Merck: Speakers Bureau.

Abstract Viral haemorrhagic cystitis (HC) is a significant complication after haematopoietic stem cell transplantation (HSCT), with a potential for major morbidity. The aim of this 7-year analysis of 1160 HSCT patients was to evaluate risk factors for the incidence, severity, toxicity of therapy, clinical course, and outcome of this condition. The overall incidence of HC was 5·8%, with most cases occurring after allogeneic HSCT. Unrelated donors (P = 0·001), non-peripheral blood stem cell source (P = 0·005), myeloablative conditioning (P<0·001), use of alemtuzumab in conditioning (P = 0·001), and severe acute graft versus host disease (P<0·001) were independent risk factors for an increased incidence of HC post-allogeneic transplant on multivariate analysis. Severe forms of HC were associated with grades II–IV acute graft versus host disease and a longer duration of haematuria. Contrary to previous studies which were carried out on smaller patient populations, busulphan, cyclophosphamide, anti-thymocyte globulin, and total body irradiation were not found to independently increase the risk of viral HC, unless used in a myeloablative combination. Neither duration of viriuria nor peak viral load in urine influenced the severity of HC on multivariate analysis. Severe HC contributed to the deaths of two patients. Overall survival was not statistically different between patient subgroups with non-severe and severe HC.

We read with interest the data from Grey-Davies et al, which demonstrates the activity of the combination of bendamustine, thalidomide and dexamethasone in a proportion of multiply relapsed cohort of myeloma patients. We have previously published the safety and activity of this combination in myeloma patients with renal impairment (Ramasamy et al, 2011). However, the optimal dose of bendamustine in combination with thalidomide and dexamethasone is yet to be defined. We used a fixed dose of 120 mg of bendamustine per cycle, which was tolerated well, with Grade 3/4 haematological toxicity in two out of nine patients. In this heavily pre-treated cohort with pre-existing cytopenias, 39% emergent Grade 3/4 haematological toxicity was observed at a cumulative median bendamustine dose of 390 mg/m2. We hope the current Myeloma UK (MUK one) trial, a Phase II randomized bendamustine dose-finding study in combination with thalidomide and dexamethasone, will shed light on a dosing strategy.

Abstract Abstract 1348 Background: There has been an improvement in the population based survival of patients with MM in the UK (Office of National Statistics), however, because of the way the data is collected it is uncertain what has happened to the outcome of younger patients. High dose melphalan with ASCT has formed an integral part of the treatment of younger patients with myeloma for more than 20 years. During this time the context within which this treatment has been delivered has changed. Peripheral blood stem cell harvesting has replaced bone marrow harvesting, and importantly, novel agents have become available at induction and at relapse. It is not known how these changes have affected patient outcome. We analysed the survival of patients undergoing ASCT for MM in a single referral centre over an 18 year period to assess the impact of these changes. Patients: 1291 patients with myeloma were registered on the Royal Marsden Hospital Database in the period between 1981–2009, of which 875 patients underwent autologous transplantation. Bone marrow transplant (BMT) was performed in 191 patient, while 684 patients had peripheral blood stem cell transplant (SCT). Prognostic Factors: The following factors were found to be associated with improved overall survival (OS) in univariate analysis: Salmon Durie Stage A vs Stage B (p<0.004), ISS Stage I vs II vs III (p<0.001), response to chemotherapy CR vs PR vs Other (p<0.007), Platelets >130 vs <130 × 109/L (p<0.001), Hb >10 vs <10 g/dl (p<0.001), Calcium <10 vs >10mg/dl, Albumin >35 vs <35g/L (p<0.034), B-2M >3.5 vs <3.5 mg/l (p<0.001), IgG vs IgA vs BJ (p<0.038). Variables significant in multivariate testing were: Response to chemotherapy CR vs 130 (HR 0.52; 95% CI 0.3–0.9), Calcium (HR1.7; 95% CI 1.2–2.5) and B2M (HR2.1; 95% CI 1.5–2.9). These variables were significantly associated with OS in the overall dataset, and in the subgroup of younger patients under the age of 60. Response and Survival: The overall response (OR) rate following induction chemotherapy was 84%, including 22% complete responses (CR). Following autologous SCT, CR rates improved to 42%, with an OR of 91%. Analysis of actuarial survival for the whole group of patients who had SCT showed that young patients had significantly longer survival (Median survival: <60yrs vs. >60yrs; 8.7yrs vs 6.2yrs, p<0.009). In order to assess the impact of the introduction of new therapeutic agents in, we defined groups of patients treated in five year periods: 1991–1996, 1997–2003, 2004–2009. 5 year OS was unchanged when comparing the first two cohorts. However, the cohort of patients treated from 2004–2009 were associated with significant improvement in 5 year survival rates, from 61% for the earlier quinquennia to 82% for those treated in 2004-9 (p<0.001). We also assessed the impact of the introduction of SCT compared to BMT. SCT entered routine use at this centre in 2002, and patient outcomes did not improve from 2002–2004. The improved survival after 2004 is therefore unlikely to be due to the introduction of SCT. Summary: We found that patient survival following ASCT did not change significantly during the period 1991–2004. However, since 2004 survival rates have improved significantly, and the group that benefitted most were patients under the age of 60. This time period corresponds to the incorporation of novel agents such as thalidomide, bortezomib and lenalidomide into induction and relapse regimens, and suggests that novel agents have significantly improved the outcome of younger patients with myeloma in the context of treatment with ASCT. Disclosures: Boyd: celgene: Honoraria. Davies:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ortho Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Hematologists are frequently involved with morphological analysis of centrifuged cerebrospinal fluid (CSF) for the diagnosis of malignant infiltration of the central nervous system (CNS). Although malignant cells in the CSF are most often due to underlying hematological cancers, leptomeningeal carcinomatous infiltration from a solid tumor is not uncommon. A 46-year-old lady presented with focal neurological signs suggestive of cauda equina compression. She was on adjuvant therapy for invasive ductal carcinoma of breast with expression of human epidermal growth factor receptor-2 (HER-2). MRI scan confirmed a metastatic deposit in the conus medullaris with tumor nodules in the cauda equina and diffuse meningeal enhancement. Clear CSF was obtained from a diagnostic lumbar puncture and microscopy showed the presence of 50/mm3 white cells and 10/mm3 red cells, with no evidence of infection. A centrifuged cytospin preparation of CSF stained with May-Grunwald-Giemsa (MGG) showed numerous small lymphocytes, neutrophils, metamyelocytes, and metastatic breast carcinoma cells (Image 1). The latter cells were much larger than the hematological cells, with homogeneous nuclei containing open chromatin and abundant cytoplasm with prominent blebs from the cell surface (Image 1). Six large metastatic carcinoma cells on a background of hematological cells including two neutrophils (bottom left), a metamyelocyte (top right), and numerous small lymphocytes (MGG stained CSF cytospin; ×40). HER-2 positive breast cancers are known to carry a higher risk for CNS metastasis [1]. The presence of lymphocytosis and granulocytosis in this nonhemorrhagic CSF is a likely localized inflammatory response to metastasis from the breast carcinoma.

To the Editor, Unlike with acute forms of leukaemia, fungal infections are rare in chronic lymphocytic leukaemia (CLL). Most previous reports have been on patients with prolonged neutropenia or after allogeneic stem cell transplantation (SCT). We would like to document a patient with CLL who had a fungal infection at unusual sites as a result of combination therapy with alemtuzumab (Campath-1H) and methyl prednisolone. This patient was neither neutropenic nor had he received SCT. A 65-year-old man was on treatment with alemtuzumab, methyl prednisolone and ciclosporin for relapsed CLL and autoimmune haemolytic anaemia. He had a neutrophil count of 2.7 9 10/L with normal serum levels of immunoglobulins and was hence not on prophylactic antimicrobials. He presented with acute onset of pain in his right eye and developed a partial loss of vision in his right temporal field over the next 24 h in the absence of fever or raised inflammatory markers. He was referred to a tertiary care centre for ophthalmological evaluation and management. Examination of the right eye revealed pan-uveitis with a vitreous abscess (Fig. 1). A vitreous biopsy showed infection by Aspergillus fumigatus. MRI scan of the brain revealed a 4 mm ring-enhancing lesion in the cortex of the left frontal lobe, consistent with cerebral aspergillosis (Fig. 2). Toxoplasma serology was negative. A highresolution CT scan of his chest was normal. He was treated with oral voriconazole and intravitreal amphotericin instillations complicated by vitreal haemorrhage due to thrombocytopenia. Both the fungal infection and the haemorrhage improved over the next 6 weeks and his vision cleared gradually. A repeat MRI scan of his brain showed complete resolution of the lesion. The combination of alemtuzumab and high-dose methyl prednisolone (CamPred) is now increasingly being used to treat patients with CLL refractory to purine analogues and those with deletions of the TP53 gene [1–3]. Alemtuzumab, a humanised anti-CD52 monoclonal antibody, targets both B and T lymphocytes in addition to monocytes, macrophages and a subset of antigen-presenting dendritic cells. It thus significantly impairs the immunological surveillance mechanisms against infections. Whilst on this heavily immunosuppressive regimen, a high index of suspicion against viral reactivations and fungal

This study was conducted to compare the presenting features and outcome of newly-diagnosed myeloma with and without extramedullary (EM) manifestations and to determine the optimum treatment. Seventy-five (16.3%) patients with EM involvement at diagnosis were compared with 384 cases without EM disease. EM patients had a more favourable International Staging System and a different distribution of myeloma isotypes. When adjusted according to the independent risk factors, patients in the EM group treated with chemotherapy alone had significantly shorter overall survival (OS) compared to those without EM disease receiving similar treatment. High-dose treatment (HDT) was associated with significantly improved OS in both groups; however, it had more impact on OS among EM group, overcoming the negative prognostic impact of presenting EM disease. Patients in the EM group treated with HDT have a similar outcome to those without EM manifestations treated with HDT. HDT should form an integral component of first-line treatment for patients with EM disease whenever possible.

Blastoid morphology is a rare presenting feature of myeloma which is frequently seen in patients with extramedullary myeloma and is associated with poor clinical outcome. Cell cycle active agents can be effective as treatment for aggressive myeloma and their activity enhanced by using them in combination with the anti-angiogenic agent thalidomide. DT-PACE is an example of such a regimen which we have used to treat 26 relapsed and or refractory patients with extramedullary/blastoid myeloma. The overall response rate (complete response/PR) was 59%, but despite these initial good responses, patients had a short progression free survival (PFS) and overall survival (OS). A subgroup of patients who proceeded to autologous stem cell transplant (ASCT) have a trend towards a better PFS and OS when compared with the group receiving chemotherapy alone (PFS = 10 vs. 3 months P = 0.273 and OS 10 vs. 7 months P = 0.235). Interestingly of the group who received ASCT consolidation three patients remain alive beyond 18 months. In conclusion, the clinical outcome of this group of cases is poor even when treated with the intensive regimen DT-PACE; however, a subgroup can do well if DT-PACE is consolidated by ASCT.

One-hundred-twenty consecutive adult patients aged 15–69 years (median 40) with acute myeloid leukemia (AML) excluding t(15;17) received induction therapy comprising idarubicin, high-dose cytarabine and etoposide. Planned post-induction treatment included two courses of moderate-intensity consolidation therapy followed by stem cell transplantation. 11 patients (9%) died during induction therapy. The complete remission (CR) rate with a single cycle of induction therapy was 71%. The overall CR rate, after salvage chemotherapy but excluding allogeneic transplantation for primary refractory disease, was 82%. CR rates with one cycle of therapy for patients with good, intermediate and poor karyotype were 96, 72 and 41%, respectively (P < 0.0001). The impact of karyotype on the overall CR rate was also significant (96 vs. 88 vs. 59%; P = 0.001). Overall, 84 of 98 patients (86%) attaining CR underwent autologous (n = 59), allogeneic (n = 23) or syngeneic (n = 2) hematopoietic stem cell transplantation in first CR. The 5-year overall survival (OS) of 43% (95% CI: 34–52%) was significantly influenced by the karyotype: good 73%, intermediate 41%, and poor 18% (P = 0.0001). These data suggest that the sequence of therapy employed is active in AML, but additional steps are needed to improve the outcome of patients with intermediate- and high-risk cytogenetic abnormalities.

Although usually confined to the bone marrow, extramedullary (EM) involvement has been reported in up to 15%–20% of patients with myeloma at diagnosis and develops in an additional 15% during the course of the disease. To date clinical observations on EM myeloma are based on small series of relapsed patients and results suggest that the disease course is often aggressive associated with both early progression and short survival. The purpose of this study was to compare the presenting clinical/laboratory features and outcome of newly presenting myeloma patients with and without extramedullary manifestations and to determine the optimum treatment for this group of patients. EM involvement was defined as the presence of extramedullary plasmacytomas clinically or radiologically; patients with solitary or multiple bony plasmacytomas were excluded. Among 459 newly-diagnosed symptomatic myeloma patients prospectively recorded in the Royal Marsden database, 75 (16.3%) had EM involvement. The main sites of involvement were paravertebral (56%), chest wall (15%) and subcutaneous (15%). The presence of EM disease was associated with higher haemoglobin, albumin, lower β2-M level, and consequently a more favorable ISS staging at diagnosis (p<0.05), which could be explained by the early presentation of these patients caused by the tumors. The EM group also had less IgG heavy chain type (36% vs 61.2%, p<0.001), more Bence-Jones (30.7% vs 13.8%, p<0.001) and non-secretory (9.3% vs 4.4%, p=0.09) type, and higher percentage of Lambda light chain type (47% vs 35%, p=0.05). The overall response rates to frontline treatment were similar for the two groups of patients; patients with EM disease having 45% CR, 31% PR and 24% NR compared to 47% CR, 34% PR and 19% NR in the other group. (P=0.5). In a univariate analysis for the whole group of patients, lower Hb, Alb, higher Ca, Cr, β2-M, older age, no high dose therapy (HDT) exposure and no thalidomide exposure were associated with shorter survival. There was no difference in progression free survival (PFS) and overall survival (OS) between the two groups. The OS was 62 months in patients with EM disease and 67 months in the other group (p=0.88), and the PFS was 24 vs 28 months (p=0.73). When adjusted according to independent risk factors (age, Ca, β2M, Alb, exposure to HDT and thalidomide), patients with EM disease who received conventional chemotherapy with no HDT had significantly shorter OS compared to those without EM disease who received similar treatment (p=0.046). HDT significantly improved the OS in both groups (p<0.001), however, it had more impact on OS among patients with EM disease, overcoming the negative prognostic impact of presenting extramedullary disease on the outcome of myeloma. A similar pattern was seen with PFS. In conclusion when treated optimally patients with EM disease at presentation have a similar outcome to patients without EM manifestations. Our results suggest that HDT should form an integral component of first line treatment for patients with extrameduallary disease.

The combination of bortezomib (velcade), pulsed dexamethasone and weekly cyclophosphamide (CVD) in relapsed/refractory myeloma patients induces high overall (75%) and complete (31%) response rates compared to velcade/dexamethasone (overall 47%, CR 5%) and velcade alone (overall 27%, CR 0%). The toxicity profiles including thrombocytopenia, neutropenia, and neuropathy were comparable between the groups.

Allogeneic stem cell transplantation (allo-SCT) after a reduced intensity conditioning (RIC) protocol is associated with decreased transplant related organ toxicity and mortality. Some authors have suggested that RIC allo-SCT be performed entirely in the outpatient setting. As a challenge to this hypothesis we examined the short term toxicity following RIC allo-SCT particularly focusing on duration of initial admissions and subsequent readmissions in the first 100 days post transplant. We analysed 104 consecutive RIC allo-SCT (median age: 52, range 19–67 yr; M: 69%, F:31%) performed at our institution between February 2003 and May 2007. All patients had a high risk haematological malignancy (27% Acute Myeloid Leukaemia, 20% Multiple myeloma, 20% Chronic Lymphocytic Leukaemia, 12% Lymphoma, 6% Myelodysplastic syndrome, 6% Acute Lymphoblastic Leukaemia, 6% Chronic Myeloid Leukaemia, 2% other). Conditioning was with fludarabine plus either melphalan, busulphan, cyclophosphamide or low dose TBI (2Gy). T cell depletion in vivo with alemtuzumab was utilised in 64%. Donor was matched related (39%) or unrelated (61%). Source of stem cells was PBSC (80%) or marrow (20%). GVH prophylaxis was CyA either alone or in combination with short term methotrexate. Patients were hospitalised from the beginning of the conditioning regimen until haematological and non-haematological toxicities had resolved. Eleven patients (10%) died before discharge. The median time required for achievement of neutrophil engraftment was 15 days (range 0–56). Four patients died prior to engraftment. Median duration of initial hospital admission was 31 days (range 17–192). In univariate analysis patients with Multiple myeloma were discharged earlier (p=0.001). Patients conditioned with Flu TBI were also discharged earlier (p<0.0001). Unrelated donor RIC allo-SCT were discharged later (p<0.001). Patients receiving alemtuzumab were also discharged later (p<0.001). Readmissions within 100 days of transplant were documented in 50/104 (48%). The most common reasons were non CMV infections (30%), GVHD (22%), CMV reactivation (22%) and progressive disease (9%). Patient diagnosis, stem cell source, donor type, conditioning regimen, T cell depletion and age had no significant bearing on the incidence of readmission in the first 100 days post transplant by multivariate analysis. Transplant related complications (Infections, CMV reactivation, GVHD, TTP) were seen in 73/104 (70%) within 100 days of transplant. Transplant related mortality (TRM) at 100 days was 15%. Patients who required readmission in the first 100 days post transplant had lower OS at 1 year (45% v 73%) than those who did not require readmission (p<0.001). The mean duration of readmissions in the first 100 days post transplant was 15.5 days. This had major financial implications with average bed costs of £7750 per readmission. In summary, although RIC regimens have undoubtedly widened the potential application of allo-SCT they are not without short term toxicity. Although early discharge following RIC allo-SCT has been advocated, our analysis demonstrates that the risk of readmission in the first 100 days post transplant is significant and is associated with increased costs and mortality. A full health economic analysis will be presented including a comparison with full intensity conditioning allo-SCT performed over the same period.

From August 1973 to December 2003, 1651 patients (median age: 28yr., range: 1–74 yr.; M: 982, F: 669) received stem cell transplants for haematological malignancies (Ac. Leuk: 1246, Chr. Leuk: 182, other: 223). Donor was allogeneic (n=1088), autologous (n=537) or syngeneic (n=26) and conditioning was with (n=1243) or without TBI (n=408). Primary disease was classed as high risk in 714 and low risk in 937 patients. Dose of TBI was ≤9.5 Gy (n=342), 10.5 Gy (n=613) or ≥ 10.5 Gy (n=282) delivered in single fraction (n=1015) or multiple fractions (n=222). Donor was sibling (n=900), matched unrelated (n=135) or mismatched family member (n=53). Cranial top-up radiation was used in 357 patients. Source of stem cell was marrow (n=1312), PBSC (n=320) or both (n=19). GVH prophylaxis was CyA alone (n=527), CyA with other agent (n=516) or other measures (n=45). Of all the patients 1515 received single transplant but 136 received more than one transplant. Data was analysed as of 01/07/2006. Of all the patients 897 (54.3%) survived for at least 1 yr. post transplant and the median follow-up in this group was 27yr. Second cancers developed in 50 cases with the incidence of 2.6% at 5yr (95% CI: 1.3–3.9), 7.5% at 10 yr (95% CI: 4.9–10.1) and 11.5% at 15yr (95%CI: 7.6–15.4). Site of second malignancy was brain (n=10), breast (n=6), cervix (n=3), GIT (n=2), lung (n=1), skin (n=9), sarcoma (n=3), thyroid (n=1), oral cavity (n=4), MDS (n=6), CML (n=1), ovary (n=1) and non EBV related lymphoma (n=3). In univariate analysis 10 yr. probability of developing SMN was significantly higher with chronic GVHD (5% vs. 10%, p=0.008, high risk disease (5% vs. 11%, p=0.0007), cranial RT (4% vs. 18%, p=0.015) and ALL as primary diagnosis (4% vs. 10%, p=0.06). In multi-variate analysis advanced stage disease (RR: 2.4, 95% CI: 1.3–4.2, p=0.004), Chr. GVHD (RR: 2.5, 95% CI: 1.4–4.4, p=0.003) and cranial RT (RR: 2.3, 95% CI: 1.2–4.4, p=0.01) were independently associated with increased risk of SMN. There was strong interdependence between cranial RT and ALL as primary diagnosis. It was noted that the multi-variate risk factors were different for site specific SMNs. For brain tumours cranial RT (RR: 12.8, 95% CI:2–75.5, p=0.006) and age <16 yr at the time of transplant (RR:15.7, 95% CI:1.9–130.6, p=0.011) were associated with increased risk. For epithelial malignancies Chr. GVHD (RR: 5.8, 95% CI: 2.2–15.5, p=0.0005), female sex (RR: 3.0, 95% CI:1.1–8.3, p=0.033) and advanced stage disease (RR: 3.6, 95% CI: 1.4–9.4, p=0.01) were associated with increased risk. No independent risk factors could be identified for development of skin or haematological malignancies. 25 patients have died due to SMN (49%) at a median of 31 months. Survival was significantly better in skin SMNs (85%) as compared to haematological SMNs (20%), brain tumours (30%) and epithelial SMNs (56%)(p=0.02). This single centre analysis shows that the risk of developing SMN does not relate to the type of conditioning and increases with longer follow-up. The risk factors vary for the different sites of SMNs. These patients need long term cancer screening.

A retrospective case-matched study was conducted to compare the oral regimen CTD (cyclophosphamide - thalidomide - dexamethasone) and infusional CVAMP (cyclophosphamide - vincristine - doxorubicin - methylprednisolone) as induction therapy followed by autologous peripheral blood stem-cell transplantation (PBSCT) for newly diagnosed multiple myeloma patients. The response rate after three cycles of treatment was statistically higher with CTD (n = 27) compared to CVAMP (n = 27) (89% vs. 56%, P = 0.016). Toxicity studies showed more neutropenia (grade 3/4) (4% vs. 60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability.

Lenolidamide (Revlimid®) is an oral immunomodulatory drug that has been shown to be effective for the treatment of relapsed refractory myeloma, and in-vitro laboratory studies suggest that its action may be synergistic with a number of conventional chemotherapeutic agents. The aim of this study is to assess the efficacy and toxicity profile when lenolidamide is used in combination with cyclophosphamide and dexamethasone for patients with relapsed refractory disease. Multiply relapsed patients were given Revlimid 25mg po on days 1–21, dexamethasone 40mg po days 1–4 and days 12–15, and cyclophosphamide 500 mg po days 1, 8, 15 and 21 of a 28 day cycle for a maximum of 6 cycles of treatment. Prophylaxis with acyclovir, septrin and proton pump inhibitors was routinely used, 1 high risk patient received prophylactic anticoagulation. Toxicity profiles and response were assessed every 4 weeks. To date 18 patients have been included in the study with median age of 60.5 years (range 34–76). All were heavily pre-treated with a median of 4 previous lines of therapies (range 2–8). 12 patients had received high dose melphalan, 18 patients thalidomide and 16 patients bortezomib. One case had undergone an allogeneic BMT. The median time from diagnosis to treatment initiation was 55.5 months (range 11–122). To date 81 complete courses of therapy have been given to 18 patients with median number of 5 courses (range 1–6). 8 patients experienced neutropenia with the neutophil count falling below 0.5×109/L in a total number of 14 cycles, which resulted in a dose reduction or stopping of cyclophosphamide in 8 patients. 12 patients received GCSF to maintain their neutrophil count. 5 patients required dose reduction/omit of Revlimid. 4 patients required intravenous antibiotics for neutropenic fever. The side effect profile was manageable, importantly no patient experienced sedation, constipation or worsening of peripheral neuropathy. 2 patients with a heavy myeloma load suffered a DVT, but continued on therapy achieving a PR once anti-coagulation had been commenced. 14 of the 17 patients assessable for response achieved a response with 1 CR, 3 VGPR, 8 PR and 2 MR according to EBMT criteria. The median time to response was prompt at 32 days (range 21–68). To date only 2 patients have discontinued therapy because of a failure to respond to therapy and 1 stopped due to liver toxicity. 13 patients have completed treatment and 5 still remain on treatment. The combination of CRD is effective in heavily pretreated myeloma patients and has a manageable toxicity profile. In view of the neutropenia further studies using this combination are currently being investigated using cyclophosphamide on days 1 and 8 only.