scholarly journals Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

2021 ◽  
Author(s):  
H. R. Wardill ◽  
C. E. M. de Mooij ◽  
A. R. da Silva Ferreira ◽  
I. P. van de Peppel ◽  
R. Havinga ◽  
...  
Keyword(s):  
Clinical Features ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Intestinal Injury ◽  
Haematopoietic Stem Cell ◽  
Severe Neutropenia ◽  
High Dose ◽  
Cell Transplant ◽  
Translational Model ◽  
Gut Toxicity

Abstract Purpose Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury. Methods Male Wistar rats were treated with 4–8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation. Results Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms. Conclusion We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success. Graphic abstract

scholarly journals Expanding the Indications for Ibrutinib: Complete Remission Obtained By Induction with Ibrutinib Followed By Consolidative Ahsct in Refractory Primary CNS Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5631-5631 ◽  
Author(s):  
Cassidy Brothers
Keyword(s):  
Complete Remission ◽  
Disease Progression ◽  
Salvage Therapy ◽  
B Cell Lymphoma ◽  
Salvage Treatment ◽  
Severe Neutropenia ◽  
High Dose ◽  
Cell Transplant ◽  
Curative Intent ◽  
Hematopoietic Stem

Introduction Primary central nervous system lymphoma (PCNSL) is an exceedingly rare and aggressive sub-type of Non-Hodgkin's Lymphoma. Despite initial polychemotherapy that includes High-Dose Methotrexate (HD-MTX), over half of patients will develop recurrent or refractory disease that requires salvage therapy.1 Ibrutinib, a Bruton's tyrosine kinase inhibitor, has become an alternative for salvage treatment in relapsed or refractory PCNSL (RR-PCNSL) that is particularly useful in patients who are ineligible for re-induction with HD-chemo. In RR-PCNSL, Ibrutinib led to a progression free survival (PFS) of roughly 5 months when used as monotherapy2,3 and 15 months when used as add-on therapy.4 While its role as salvage treatment has been documented, its use to facilitate consolidative autologous hematopoietic stem cell transplant (AHSCT) in RR-PCNSL is not currently known. The following case describes the first known report of a patient with RR-PCNSL who achieved persistent complete remission following Ibrutinib salvage treatment and consolidative AHSCT. Case Description A 64-year-old male presented to the emergency department with a two-week history ptosis, visual abnormalities, confusion, and increasing fatigue. On physical exam, he was found to have bilateral mydriasis, left third nerve cranial palsy, severe left-sided ptosis, and restricted upwards and downward gaze of the right eye. A contrast-CT was performed which showed multiple areas of abnormal enhancement throughout the frontal lobes, corpus callosum, and midbrain associated with significant vasogenic edema. These findings were confirmed on MRI. He underwent a stereotactic guided burr hole biopsy which was consistent with diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry performed on the tissue showed that the neoplastic cells were CD3(-), CD5(-), CD20(+), CD10(-), BCL2(subset +), BCL6(+), MUM1(+) and Cyclin D1(-). Staging CT and bone marrow biopsy showed no evidence of systemic disease. He was diagnosed with PCNSL and went on to receive induction therapy with Rituximab, Methotrexate, Procarbazine, and Vincristine (R-MPV) with curative intent and received a total of 7 cycles. Initially, he had a significant radiographic response with a repeat MRI post cycle 4 showing only a few small areas of residual enhancement. However, after completion of the 7 cycles of R-MPV, his MRI showed evidence of disease progression with both new and enlarging intra-axial lesions. Given his ECOG of 0 and lack of comorbidities, it was decided that he would proceed with salvage treatment with Cytarabine and Etoposide with curative intent for refractory PCNSL. Unfortunately, after only four weeks of receiving cycle one of Cytarabine and Etoposide, a repeat MRI showed evidence of disease progression. He was then transitioned to palliative therapy with prednisone up until December 2017, at which point he was able to obtain Ibrutinib on a compassionate basis. He was started on Ibrutinib salvage therapy and achieved radiographic evidence of complete remission after four months of treatment. There were minimal adverse effects of Ibrutinib therapy, most notably a severe neutropenia requiring a temporary discontinuation of therapy for two weeks. He underwent consolidative AHSCT with Thiotepa, Busulfan and Melphalan conditioning in August 2018. His post-transplant course was complicated by culture negative febrile neutropenia with a subsequent source determined to be Clostridium difficile for which he was treated. An MRI head performed 3 months after his AHSCT showed no evidence of recurrent or residual disease. He continues to be followed by the Hematology Service in Newfoundland and has remained in complete remission since. Conclusions This case demonstrates the feasibility of a salvage approach using Ibrutinib followed by AHSCT when standard salvage options have been exhausted in refractory PCNSL. OffLabel Disclosure: Ibrutinib's indications do not currently include use as a induction treatment prior to AHSCT in refractory/recurrent PCNSL.

scholarly journals Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

2012 ◽  
Vol 6 (2) ◽  
pp. 14 ◽  
Author(s):  
Catriona Elizabeth Mactier ◽  
Md Serajul Islam
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Treatment Plan ◽  
Allogeneic Transplantation ◽  
Global Perspective ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Combination Regimen ◽  
Cell Transplant

Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-<em>versus</em>-myeloma effect may offer a potential <em>cure</em> for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

MECp, a Salvage Regimen with Drugs Not Employed as Frontline Therapy, Allowed to Obtain a High CR Rate and to Bring to Unrelated Allogeneic Transplantation a High Proportion of Adult Patients with Relapsed ALL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4101-4101
Author(s):  
Erika Borlenghi ◽  
Elisa Cerqui ◽  
Chiara Cattaneo ◽  
Francesco Zuccalà ◽  
Piero Galbiati ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Adult Patients ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Cell Transplant ◽  
First Line ◽  
Salvage Regimen ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 4101 Background and aim The only curative option for adult patients with refractory or relapsed ALL is allogeneic haematopoietic stem cell transplant (allo-HSCT), which can offer a 28-34% long term survival in transplanted patients. However the actual feasibility of allo-HSCT is only 20-30% in unselected patients because of the low rate (30-50%) of complete remission (CR) achieved with salvage regimens (Tavernier, 2007- Thomas, 1999), the high rate of early relapse (Martino, 1999) and the difficulties in finding a suitable donor before progression (Davies, 1996). Hence, relapsed ALL can be actually cured in less than 10% of unselected adult patients. Using a second line treatment capable of obtaining a higher proportion of CR of longer duration may improve the dismal overall prognosis of patients. We report on the efficacy and toxicity profile of the combination of 6-metilprednisolone, mitoxantrone, etoposide and high-dose cytarabine (MECp), a salvage regimen containing cytostatic drugs to which patients had not been exposed during first line therapy, except for cytarabine at lower doses. Patients and Methods Between October 2000 and May 2009, 18 refractory/relapsed ALL patients were treated at our Institution with MECp regimen, consisting of a single course of etoposide 80mg/mq/die iv, cytarabine 1000mg/mq/die iv for 6 hours and mitoxantrone 6mg/mq/die iv 9 hours after cytarabine infusion for 6 days associated to metilprednisolone 50 mg/mq/die for 21 days, subsequently tapered to zero over one week. Three patients received an experimental sequential pulsed chemotherapy program in a multiinstitutional setting. At diagnosis, all patients had been treated according to the NILG-ALL 00/09 program (Bassan, Blood 2009). Four had been refractory to induction therapy and 14 had relapsed after a median of 12 months (range 3-43), 11 while on consolidation/maintenance, one after allo-HSCT, two after 3 and 12 months from the end of maintenance. There were 10 males and 8 females with a median age of 28 (range 17-64). ALL lineage was B in 9 cases (4 pro-B, 4 common, 1 pre B), T in 8 (5 pro-T, 3 cortical-TIII) and biphenotypic in 1. Molecular studies showed MLL/AF4 rearrangement in 3 and bcr/abl rearrangement in 3 cases, all before tyrosine-kinase inhibitors were available. Karyotypic abnormalities were present in 10 of 16 evaluable cases. Patients were treated in single/double bed rooms with reverse isolation. In 3 cases treatment duration was reduced to 4 days. Results CR was obtained in 13 of 18 patient (72,2%), independently of immunophenotype and time to relapse. CR rate was 100% in all ten patients with karyotypic abnormalities. Three patients (16%) died in aplasia during treatment, 2 of septic shock and 1 of unexplained shock. Two patients (T-ALL) were resistant. Recovery of neutrophils (>0,5×109/L) and platelets (>20×109/L) required a median of 22 days (range 17-37) and 28 days (range 21-45) from the start of therapy, respectively. Infections were documented in 9 of 18 (50%), being fatal in 2 (11%). Non-haematologic toxicity, mainly mucositis, was negligible. The median duration of CR was 5 months (range 2-5) which allowed 9 of 13 CR patients (69%) to undergo allo-HSCT (7 MUD, 1 HLA-identical sibling and 1 cord blood) after a median of 4 months (range 2-7) from CR. Reason for not being transplanted was failure of donor search in 4 patients who relapsed a median of 4 months. Causes of death included progressive disease in 7 patients, in 3 cases after HSCT, and transplant-related toxicity in 3 patients. The median survival of patients achieving CR was 13 months (range 7-33) and overall survival of the entire cohort was 8 months (range 1-33m). Conclusions With MECp, a combination of drugs not used during previous first-line therapy, a higher CR rate (72%) than commonly reported could be obtained, with acceptable toxicity. CR duration was long enough to allow 44,4% of patients to receive a non-family donor allo-HSCT, which is presently the best, yet still unsatisfactory, treatment option for adult patients with refractory/relapsed ALL. Disclosures: No relevant conflicts of interest to declare.

Cerebral Toxoplasmosis in a Patient with Prolonged CD4 Lymphopenia Post Autologous Haematopoietic Stem Cell Transplant

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4902-4902
Author(s):  
Arielle van Mourik ◽  
Andrew P Grigg
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Additional Risk Factor ◽  
Average Dose ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cerebral Lesions

Abstract Toxoplasma gondii is a ubiquitous protozoan parasite which infects approximately one third to one half of the world's population. In the immunocompetent host it typically causes a self limiting and asymptomatic infection before entering a lifelong latent phase. Reactivation and disseminated toxoplasmosis occur in the setting of impaired cellular immunity as described in patients with acquired immunodeficiency syndrome (AIDS) secondary to human immunodeficiency virus (HIV) infection and those receiving prolonged immunosuppression post solid organ or allogeneic haematopoietic stem cell transplantation. Toxoplasmosis post autograft has been rarely described. We present a case of toxoplasma encephalitis in a patient with persistent CD4 lymphopenia post autograft for peripheral T-cell lymphoma (PTCL). A 64y HIV negative female was diagnosed with autoimmune haemolytic anaemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) in 2012 and 2013, treated with intravenous immunoglobulin (IVIg), 4 months in total of prednisolone (two separate courses, average dose 30mg/day), a single dose of 375mg/m2 rituximab and 6 months of azathioprine 100mg/day. The lymphocyte count prior to AIHA was normal (2.9 x 109/L; normal range 1-4 x109/L). The subsequent course was complicated by persistent lymphopenia in the absence of immunosuppression (0.3-0.7x109/L,) and cutaneous mycobacterium kansasii infection. PTCL was diagnosed in February 2015 and treated with 6 cycles of high dose chemotherapy (CHEOP) followed by an autograft in July 2015 with BEAM conditioning. Lymphocyte counts at 3, 7, 9 and 12 months post transplant were 0.4, 0.5 ,0.8 and 0.3 x 109/L respectively. Dapsone for pneumocystis jirovecii pneumonia (PJP) prophylaxis was given; cotrimoxazole was contraindicated due to a rash. Twelve months post autograft she developed left leg weakness and intermittent headache. A MRI brain showed 4 enhancing cerebral lesions, of which histology demonstrated toxoplasma tachyzoites in neutrophils confirmed by PCR. Toxoplasma serology was IgG positive but IgM negative. The CD4 count was severely reduced 0.09 x 109/L (normal 0.65-2.0 x 109/L) as were other lymphocyte subsets (CD8 0.04 x 109/L (0.33-1.3), NK 0.03 x 109/L (0.13-0.54) and B cells 0.13 x 109/L (0.19-0.55). Immunoglobulin levels were normal. Treatment with pyrimethamine and sulfadiazine was commenced with some improvement in neurology prior to discharge for rehabilitation. Toxoplasmosis occurring more than 2 months post autograft is very rare, with to our knowledge only 9 cases previously reported. Of these, 6 of the 8 evaluable documented an additional risk factor for reactivation including persistent lymphopenia (one case attributable to CD34 selection), etanercept and high dose steroids. In our case the main risk factor appeared to be pre-existing (historically most likely auto-immune mediated (Regent, Medicine 2014)) and persistent post-autograft lymphopenia with particularly low CD4 levels. After an autograft, CD3 counts can be expected to return to baseline by three months but CD4 counts recover more slowly and incompletely by 12 months (meanat 1, 3, 6 and 12 months: 0.22, 0.27, 0.38 and 0.46 x 109/L respectively (Damiani, Ann Oncol 2003) Post autograft, no prophylaxis or screening for toxoplasmosis infection is recommended (Tomblyn, Biol Blood Marrow Transplant 2009). However, when warranted, the drug of choice is cotrimoxazole, often concurrently administered for PJP prophylaxis. In practice due to myelosuppression or rash, cotrimoxazole is frequently replaced by dapsone or pentamadine, neither of which is proven to be effective against toxoplasma. This case highlights a need to review current guidelines and consider prophylaxis for toxoplasmosis in patients at high risk of reactivation post autograft, such as those with persistent lymphopenia and high dose steroids. Disclosures No relevant conflicts of interest to declare.

scholarly journals Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

2012 ◽  
pp. e14
Author(s):  
Catriona Elizabeth Mactier ◽  
Md Serajul Islam
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Treatment Plan ◽  
Allogeneic Transplantation ◽  
Global Perspective ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Combination Regimen ◽  
Cell Transplant

Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

scholarly journals POEMS Syndrome: Demographics and Outcomes in a United Kingdom Cohort

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5582-5582
Author(s):  
David Foldes ◽  
Stephen Keddie ◽  
Stephanie Baldeweg ◽  
Mary Reilly ◽  
Kwee L Yong ◽  
...  
Keyword(s):  
United Kingdom ◽  
Stem Cell ◽  
Data Collection ◽  
Diagnostic Criteria ◽  
Clinical Features ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Limited Disease ◽  
Sustained Improvement ◽  
The United Kingdom

Abstract Introduction POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) syndrome is a rare multi-system disorder characterised by a monoclonal plasma cell disorder and peripheral neuropathy in combination with a myriad of other clinical features. Several patient cohorts have previously been described leading to the formulation of diagnostic criteria. For the purposes of establishing a specialist centre in the United Kingdom we collected data of our patient cohort and compared it with previous reports. Methods Demographic data for patients currently known to our clinic with an established diagnosis of POEMS (n=52) was extracted from an already existing database. Clinic letters for these patients were retrospectively screened for clinical features, diagnostic criteria, treatments given and response to treatment, occasionally supplemented by review of historical investigation results. The data was collected in a newly established database designed to facilitate future prospective data collection. Results Our cohort currently consists of 52 patients from a mixed ethnic background, with a male to female ratio of 4.2:1 (n=42 vs 10 respectively) and a median age of 57; median age at diagnosis was 49. The majority of patients were referred to our centre from across the United Kingdom between 2009 and 2015. The prevalence of diagnostic criteria broadly resembles previously published cohorts (see table). 17 patients received radiotherapy for limited disease while 31 patients underwent autologous haematopoietic stem cell transplant (ASCT); 18 patients received at least one line of systemic chemotherapy. A subgroup review of patients who underwent ASCT showed sustained clinical improvements in 83% of patients reviewed; 61% of patients who received radiotherapy had a documented sustained improvement. Patients receiving chemotherapy showed a more variable response; of note, 4 out of 6 patients treated with a combination of lenalidomide and dexamethasone were documented to have had significant clinical improvement. 3 patients died during the period of follow-up at the ages of 70, 63 and 63, respectively. Death occurred between 4 and 15 months following diagnosis; none of the deceased patients underwent ASCT or radiotherapy. Discussion We report the basic demographic and clinical outcomes of a new cohort of patients with this rare condition. Our cohort broadly resembles other previously published reports, as does our experience with therapeutic options. Radiotherapy appears to be effective in stabilising or improving limited disease confined to a solitary plasmacytoma or few lytic foci, while autologous stem cell transplantation achieves sustained improvement in the majority of patients with more diffuse disease. Chemotherapy offers further treatment options for patients not suitable for either of those, with lenalidomide becoming an increasingly promising agent. Retrospective data collection and the establishment of a database for prospective study will enable us to further investigate this group with a view to expand our understanding of this poorly understood disease. Disclosures Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

scholarly journals Melphalan 140 Mg/m 2 As Conditioning Regimen for Autologous Stem Cell Transplant- Comparative Study from a Tertiary Centre in Southern India

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5024-5024
Author(s):  
Sani Kodathumuriyil Sunny ◽  
Nikhil Krishna Haridas ◽  
Remya Sudevan ◽  
Ambily Nadaraj ◽  
Manoj Unni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Haematopoietic Stem Cell ◽  
Categorical Variables ◽  
High Dose ◽  
Cell Transplant ◽  
Female Ratio ◽  
Neutrophil Engraftment

Abstract Background: High-dose chemotherapy (HDT) followed by autologous haematopoietic stem cell transplantation (ASCT) is the standard consolidation therapy for eligible patients with newly diagnosed Multiple myeloma (MM).Many trials have demonstrated the superiority of ASCT over non-intensive approaches, patients had received high-dose chemotherapy with melphalan at a dose of 200mg/m 2 (Mel200).Some studies had associated Mel200 with increased toxicities Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study showed that outcomes were similar in Mel140 vs Mel200 when patients were in partial response (PR) or better. In this study,we looked at the outcomes and safety of conditioning regimen used at two different doses of Melphalan for patients who had achieved PR. Methods: This retrospective study comprised of patients treated in our hospital between January 2013 and December 2020. Patients with MM who had achieved PR, very good partial response (VGPR) or complete response (CR) as per standard IMWG response criteria at ASCT were included . Mel 140 and Mel200 were used for consolidation treatment. Patients who received other doses were excluded. Variables assessing safety namely neutrophil engraftment (defined as first of 3 successive days with an absolute neutrophil count of &gt;/=0.5x10 9/L after post-transplant nadir), platelet engraftment (defined as first of 3 consecutive days with count &gt;/=20 x10 9/L in absence of platelet transfusion for 3 days), days of hospital stay, quantity of PRBC and platelets, febrile neutropenia episodes and number and duration of antibiotic therapy and variables assessing outcome namely Progression Free Survival (PFS) were compared between the two groups. Categorical variables were analysed using Chi-Square/Fisher test, exact and continuous variables using student's T-test /Mann-Whitney Test. Kaplan-Meier (KM) plot was generated to depict PFS. A Breslow test was run to determine difference between survival distributions. All analysis used SPSS 22 version and a p value of &lt; 0.05 was considered statistically significant. Results: The study included fifty seven patients (n=57) who underwent ASCT with a median follow up of 110 ± 12.3 months . Male / Female ratio was 1.48:1 and the mean age was 52.4 (28-66).Patient characteristics are described in table 1. The disease status at time of transplant was PR 16(28%), VGPR 25 (43.8%) and CR 16 (28%). GCSF alone was used for stem cell mobilisation in 29 patients (50.8%), GCSF + Plerixafor in 26 (45.6%), GCSF + cyclophosphamide in 2 (3.5%). The median CD34 count was 5.2 (1.49 - 19) x 10 6cells/ml. The median time to neutrophil engraftment was 9.5 (8 - 21) days and to platelet engraftment was 10.5 (7 - 40) days . The estimated PFS by KM plots showed a median survival of 42.5 +/-5.2 months. On comparative analysis of patients who received Mel200 vs Mel140, both the groups had similar demographic characteristics and disease outcomes (Table 1).Patients who received Mel 140 received significantly less number of packed red blood cell units (PRBC) [1 (0-1) vs 2 (1-5), P = 0.022] and platelets [9 (1-5) Vs 10(1-19), P&lt;001].These patients also had faster platelet engraftment (P =0.004) and lower incidence of Mucositis[9.7% vs 61.5%, P &lt; 001] reflecting a favourable toxicity profile of this dose. However, the lower dose does not seem to affect disease outcome since PFS was similar in Mel 200 and Mel 140 (42.6 ± 4.8) Vs (42.8 ± 6.3) months [Figure 1] Conclusion: For patients with MM who achieved PR , VGPR and CR prior to ASCT, Mel140 had similar PFS as Mel200 with lesser toxicities like mucositis, faster platelet engraftment and reduced blood product and antibiotic usage . Even though the study is limited by a smaller cohort and retrospective design, the results suggest the need for a prospective randomised controlled trials to compare Mel140 and Mel200 in patients achieving PR or more prior to ASCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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