scholarly journals Second Malignant Neoplasms (SMN) in Myeloma Patients Post Stem Cell Transplant (SCT)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1839-1839
Author(s):  
Samar Kulkarni ◽  
John Murray ◽  
Jim Cavet ◽  
Mike Dennis ◽  
Adrian Bloor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Solid Tumours ◽  
Malignant Neoplasms ◽  
High Dose ◽  
Cell Transplant ◽  
Treatment Needs ◽  
Increased Risk ◽  
Long Term Consequences

Abstract Introduction: Recent developments in management of patients with myeloma have resulted in longer survival. Availability of newer class of agents for treatment has prolonged survival, improved quality of life and achieved better disease control. Use of SCT, either autologous (AutoSCT) and to a lesser extent allogeneic (AlloSCT) still forms an important aspect of myeloma treatment pathway. Improved survivorship mandates evaluation of long term consequences and risk of SMN is one of the most important long-term consequences affecting overall outcome. Aim: Estimate the risk of SMN post SCT in patients with Myeloma. Methods and Materials: Analysis includes 779 patients who received SCT for myeloma from January 2002 to December 2019. Data was collected using case records, electronic patient records, transplant database and information from referring hospitals. Follow-up was updated to June 2020. Results: Analysis includes 779 patients with myeloma (M: 488, F:291; median age:59yr, range: 26-75) receiving AutoSCT (n=716) or AlloSCT (n=63). Conditioning for AutoSCT was high dose melphalan in majority (n=714, 99.7%). AlloSCT conditioning was RIC (n=40/63, 63.5%) or MAC (n=23/63, 36.5%). TBI was part of conditioning in 51/779 (6.5%). There was no difference in demographics between two groups. Results: Median follow-up was 46 mo (range: 0.2-220). Second malignancy was identified in 48 of 779 cases (6.0%). SMN developed in 6/63 (10%) AlloSCT and 42/716 (6%) AutoSCT patents (p=0.25). SMN types were haematological (n=21), lymphoma (n=6) and solid tumours (n=21). MDS was the only haematological SMN in this series. Secondary MDS developed in 20/21 of AutoSCT as compared to 1/63 in AlloSCT (p=0.01). Non-haematological SMN were breast (n=3), upper GI (n=3), lower GI (n=2), hepato-billiary (n=2), prostate (n=3), skin (n=5), and unknown primary (n=1). SMN incidence was higher with increasing follow-up (2002-2014, 8%; 2015-2017, 2.8%, 2018-2019, 0%, p=0.002). There was no association with development of SMN and gender, age at transplant, type of stem cell source or transplant conditioning. Incidence of SMN was significantly higher for all sites as compared to general population. Cumulative incidence of SMN was 5% at 5 yr, and 15% at 10 yr for AutoSCT patients. Conclusion: Myeloma patients are at increased risk of SMN and need monitoring for long term side effects. Development of MDS post AutoSCT is the commonest SMN post AutoSCT but there is increased incidence of solid tumours as well. Impact of new modalities of treatment needs long term monitoring. Disclosures Bloor: Novartis: Honoraria; Kite, a Gilead Company: Honoraria.

A major health problem facing immigrant children: nutritional rickets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Erdal Kurnaz ◽  
Semra Çetinkaya ◽  
Selin Elmaoğulları ◽  
Aslıhan Araslı Yılmaz ◽  
Nursel Muratoğlu Şahin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immigrant Children ◽  
High Dose ◽  
Pediatric Endocrinology ◽  
Major Health Problem ◽  
Nutritional Rickets ◽  
Increased Risk ◽  
Long Term Follow Up

Abstract Objectives Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic. Methods Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records. Results Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases. Conclusions The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children.

Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5234-5234
Author(s):  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Stephen J. Schuster ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Tumor Cells ◽  
Platelet Transfusion ◽  
High Dose ◽  
Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1038-1038
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Allogeneic Stem Cell Transplant

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplant for Myasthenia Gravis: A Single-Centre Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3996-3996 ◽  
Author(s):  
Adam Bryant ◽  
Elizabeth Pringle ◽  
Christopher Bredeson ◽  
David S. Allan ◽  
Grizel Anstee ◽  
...  
Keyword(s):  
Emergency Department ◽  
Stem Cell ◽  
Myasthenia Gravis ◽  
Targeted Therapies ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Autoimmune Conditions ◽  
Life Threatening

Abstract Myasthenia Gravis is an antibody-mediated disease that affects the neuromuscular junction. Despite advances in immune-targeted therapies, a subset of patients demonstrate refractory disease with severe or life-threatening symptoms. Disease control has been achieved using autologous hematopoietic stem cell transplant (HSCT) in a variety of autoimmune conditions including multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, stiff person syndrome, and others. Here we report our center’s experience using autologous HSCT in seven patients with myasthenia. Seven myasthenia patients underwent HSCT between 2001 and 2011. Six patients were female. Median age (range) was 37 at diagnosis (17-52) and 43 at HSCT (24-55). Before HSCT, myasthenia severity, standardized by the Myasthenia Foundation of America (MGFA) clinical classification, was graded as moderate in 2 patients, severe in 3 patients, and life-threatening in 2 patients. Treatment regimens included pyridostigmine in all patients, and immune-targeted therapies including: steroid therapy in all patients, an additional immunomodulating drug in 6 patients, and plasma exchange or intravenous immunoglobulin in all patients. All patients had at least one myasthenia-related emergency department visit or hospitalization prior to HSCT, 3 requiring ICU stays and 2 requiring intubation. All patients underwent HSCT mobilization with cyclophosphamide and filgrastim. Stem cells were harvested from peripheral blood and selected for CD34+ cells in all cases. Conditioning regimens used busulfan, cyclophosphamide, and antithymocyte globulin (Bu-Cy-ATG) in 4 patients, Cy-ATG and total body irradiation in 2 patients, and etoposide, melphalan and dexamethasone in 1 patient who was undergoing HSCT for relapsed follicular lymphoma (FL). Median post-HSCT follow-up was 40 months (range 29-149). At last follow-up MGFA postintervention status was classified as complete stable remission (CSR) in all patients, indicating patients bad been experiencing no myasthenia symptoms and were on no myasthenia therapy for at least one year. Six patients had no further hospitalizations or emergency department visits post HSCT. One patient required hospitalizations in the 6 months post HSCT but at time of writing had been not hospitalized for myasthenia for more than 10 years. One patient died 29 months post HSCT from relapsed FL. At time of death this patient’s myasthenia was in CSR. There were no HSCT regimen-related deaths. No patients required ICU care during HSCT admission. Absolute neutrophil count exceeded 0.5 x 109/L on median post HSCT day 11 (range 13 - 28). Median hospital stay, including administration of conditioning regimen was 34 days (range 20-43). In the first post-HSCT year the cohort experienced 6 viral reactivations in 3 patients: 3 cases CMV viremia, 1 case BK virus-induced hemorrhagic cystitis, 1 case VZV dermatitis, 1 case oral HSV. Two late post-HSCT complications were observed: one case of acquired amegakaryocytic thrombocytopenia (post-HSCT day 701), and one case of relapsed FL (post-HSCT day 846) resulting in patient death. HSCT resulted in longstanding symptom- and treatment-free remission in seven patients with refractory myasthenia gravis. The procedure was tolerable however the intense immune depletion transiently increased risk of viral reactivation. This experience demonstrates that in selected myasthenia gravis cases, HSCT is a viable option for long-term disease control. The novel application of HSCT for this and other autoimmune conditions is an area that warrants further exploration and long-term follow-up. Disclosures No relevant conflicts of interest to declare.

Mantle cell lymphoma (MCL): Induction therapy with HyperCVAD/High-dose methotrexate and cytarabine (M-C) (±rituximab) improves results of autologous stem cell transplant in first remission

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
J. Vose ◽  
F. Loberiza ◽  
P. Bierman ◽  
G. Bociek ◽  
J. Armitage
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Disease Free Survival ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Disease Free

7511 Background: Although patients (pts) with MCL have a high response rate to standard chemotherapy, they continue to relapse with no plateau in long term disease-free survival. The use of dose intense induction therapy such as HyperCVAD (M-C) ±Rituximab(R) and high-dose therapy and stem cell may improve these results. In this analysis the outcomes of pts receiving a standard anthracycline induction therapy or HyperCVAD(M-C)(±R) then followed by a stem cell transplant in first complete (CR1) or partial remission (PR1) were compared. Methods: Between 6/91 and 11/05, 124 pts with MCL received high-dose chemotherapy and a stem cell transplant. Of these pts, 80 received an autologous stem cell transplant in CR1 (N = 47) or PR1 (N = 33). A standard anthracycline based CHOP-like (±R) induction therapy was given to 48 pts compared with 32 pts who received HyperCVAD(M-C)(±R) prior to transplant. Results: The median age of pts was 56 years (range 33–70). The male:female ratio was 33:57. Bone marrow involvement prior to conditioning was present in 52% of pts. An elevated lactic dehydrogenase (LDH) was present in 58% of pts. 65% of patients received one prior chemotherapy before coming to stem cell transplant. The median follow up of pts is 38 months (range 3–143). Progression-free survival (PFS) and overall survival (OS) are outlined in table 1 . Characteristics associated with an improved OS by multivariate analysis included receiving HyperCVAD induction (p = 0.04), transplant in CR1 (p = 0.009), ≤ 3 prior chemotherapy regimens (p = 0.02) and no B symptoms at transplant (p = 0.05). Conclusions: To improve the long term disease free survival for pts with MCL, Hyper-CVAD(M-C)(±R) induction should be given to eligible patients with autolgous stem cell transplantation in CR1. [Table: see text] No significant financial relationships to disclose.

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