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Multiple Myeloma in Patient with Co-existing Chronic Renal Failure on Hemodialysis: A Case Report
abstracts designed clinical trials are warranted to identify not only lymphoma-related factors but also host factors for survival.
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Guillermo O. Rocabado Calizaya, Astrid S. Riveros, Almazan Leyton Omar Department of Onco Hematology, Children’s Hospital "Dr. Ovidio Aliaga Uria", La PazBolivia, Bolivia, Plurinational State of Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in the pediatric age, treated efficiently and in cases of low risk it is possible to obtain a cure of up to 80%. However, some low-risk patients die from complications secondary to drug toxicity. In Bolivia, administering MTX at high doses represents a risk of intoxication because serum levels of the drug can not be determined for the corresponding rescue, so the optimal doses should be reduced in these high-risk patients. Equipment: Methotrexate MTX lyophilized powder. LVO leucovorin. TEAMS RMN, Bruker AVANCE AV-500 CHROMATOGRAPH HPLC, Waters: Alliance, with UV detector. Population in Study: 10 children, eight male and two female, selected at random from a targeted population. Methodology: Plasma of whole blood was used. The isocratic separation was implemented a K-C18 column (kromasil) with a mobile phase consisting of buffer of 50 mM sodium acetate (pH 3.6), acetonitrile (89:11, v / v). Results and Conclusions: High doses of MTX, start from 2000 mg to 8000 mg, children should receive the correct rescue with LVO, in this work it was shown that the concentrations prove to be inappropriate, since the start of the rescue with 0.0021 ng / ml of LVO, coincides with the highest dose of MTX of 0.16679344 ng / ml. The follow-up of the patients showed that the therapy was concluded as follows: mucositis grade 2 to 3, between days 5 and 7 after the rescues with LVO ended, this shows that the rescue and recovery should be delayed for at least 3 to 5 hours. to readjust the dose of LVO to finish with a higher dose to decrease the toxic effect of MTX. Analysis by Nuclear Magnetic Resonance: The LC signal overlaps in the sample could lead to doubt regarding a masking of the LVO peak by MTX or metabolites that have retention times between 11 and 14 minutes, which is why it was decided to apply the chemical technique of NMR-C13 which rules out the interference hypothesis.
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Targeting of versican, a proteoglycan in bone marrow microenvironment by microRNAs inhibit multiple myeloma progression
Nidhi Gupta1, Raman Kumar1, Tulika Seth2, Bhavuk Garg3, Alpana Sharma1 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India, 2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India, 3 Department of Orthopedics, All India Institute of Medical Sciences, New Delhi, India
1
Background: The abnormal growth of malignant plasma cells in Multiple myeloma (MM) require bone marrow (BM) niche consisting of proteoglycans, cytokines, etc. for their growth. One of the chondroitin sulfate proteoglycan, Versican (VCAN) has gained consideration in milieu of solid tumors but there is dearth of literature in MM. Hence, involvement of VCAN in MM and its regulation by microRNAs has been studied. Materials and Methods: 30 MM patients & 20 controls were recruited and BM Stromal Cells (BMSCs) were harvested by primary culture. Molecular expression of VCAN and microRNAs (miR-144, miR-199 & miR-203) were examined in study subjects and MM cell lines (RPMI8226 & U266). The involvement of VCAN in myeloma pathogenesis was studied using BMSCs conditioned medium (BMSCs-CM) and VCAN-neutralizing antibody or microRNA mimics (miR-144 and miR-199). Further, signaling pathways altered by knockdown of VCAN by antibody or microRNA mimics were identified. Results: Elevated expression of VCAN was found in MM patients especially in the stroma of BM niche while microRNA expression was lower in patients and showed negative correlation with VCAN levels. VCAN being produced in stroma found at lower levels in MM cell lines. Moreover, BMSCs CM showed presence of VCAN which upon supplementing to MM cells alter parameters in favour of myeloma progression, however, this effect was neutralized by VCAN antibody or miR mimics of miR-144 and miR-199. The downstream signaling of VCAN was found to activate FAK and STAT3 which subsides by using VCAN antibody or miR mimics. Conclusion: The neutralization of oncogenic effect of BMSCs CM by VCAN blockage using antibody or miR mimics affirms its plausible role in progression of MM. These findings open up new avenues for exploring VCAN as a novel therapeutic target and microRNAs as a mean to target VCAN which could be exploited in clinical settings in future.
vi122 | Poster Session
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Multiple Myeloma in Patient with Co-existing Chronic Renal Failure on Hemodialysis: A Case Report
Noorwati Sutandyo, Nia Novianti Hematology and Medical Oncology Department, Dharmais National Cancer Centre Hospital, Indonesia Background: Impaired renal function in multiple myeloma (MM) patients is common and will generally improve after treatment. However, some patients showed no improvement after therapy, thus, other causes of renal impairment must be suspected. Case Illustration: This is a case about a 57-year-old male MM patient with co-existing chronic renal failure due to chronic pyelonephritis and hypertension. Patients underwent routine hemodialysis twice a week and received intravenous bortezomib 1.3 mg/ m2 a day after hemodialysis, melphalan 9 mg/m2 and oral prednisone 60 mg/m2 day -1 to -4. However, there was no significant improvement in renal function. After undergoing three cycles of chemotherapy, patients experienced worsening due to sepsis, deteriorating renal function and death. Conclusion: It is a challenge to make early diagnosis and choose appropriate treatment in multiple myeloma patients with co-existing chronic renal failure. Management of MM with chronic renal failure includes supportive therapies and treatment of myeloma using the latest generation of drugs.
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Rapid improvement of secondary myelodysplastic syndrome from essential thrombocytosis (ET) treated by Azacitidine(AZA)
Masahide Yamazaki Keiju General Hospital Background: It is well known that secondary MDS is refractory to treatment. In general, high-risk MDS is treated with AZA, but its effect is often delayed. I experienced a case which has rapidly improved to the ET from secondary MDS after 2 courses of AZA. Case report: A 70 - year - old woman, who had diagnosed with ET 20 years before and treated with hydroxyurea for 5 years, was admitted to our hospital with pancytopenia. On abdominal CT, it showed splenomegaly. In chromosome testing showed complex karyotypes. Plasma WT-1 level showed a significant high as 96000 copy. In bone marrow aspiration, blasts together indicate to the atypical three strains accounted for 18%, was diagnosed with secondary MDS (RAEB-t, IPSS-R: 9.5 points). Bone marrow biopsy was similar findings and myelofibrosis was not observed. She was treated with AZA at a dose of 75 mg / m2 over a 7-day subcutaneous injection, and was followed for 3 weeks. She withdrawal from transfusion-dependent in the initial treatment, and at the time of 2 the end of the course, her WBC number (990 / ml to 7240 / ml) and Hb level (6.3 g / dl to 13.8 g / dl) were normalized, and her blood platelet count was markedly increased from 56,000 / ml to 1,340,000 / ml. Plasma WT - 1 level decreased markedly from 96000 copies to 430 copies, and the splenomegaly also improved on US study. Bone marrow aspiration showed hyperplastic bone marrow accompanied by a marked increase in megakaryocytes, the three line heterozygosity disappeared, and the blasts decreased to 1.2%. Even in bone marrow biopsy consistent with ET. Discussion: Secondary MDS developed with chemotherapy is generally often refractory to treatment. In our case, we withdrew from transfusion dependence with firsttime AZA therapy and improved to ET, the original disease at the end of 2 courses. Secondary MDS patients who respond with small number of AZA therapy are extremely rare and are valuable cases.
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An unexpected but successful pregnancy for young lady with CML
Hirofumi Yokota, Yuichiro Inagaki, Yuki Takeuchi, Shihomi Kuwano, Hitomi Sawa, Kanae Imai, Tomonori Kato, Masashi Sawa Anjo Kosei Hospital Background: The prognosis of CML has dramatically improved with the introduction of imatinib. Patients diagnosed in chronic phase can live almost as long time as healthy people. However, adequate strategy of pregnancy under TKI treatment has not been established. Case report: 31-year-old-female was introduced to us because of leukocytosis. She was diagnosed as CML CP. We let her visit OB-GYN clinic with her partner to preserve a fertilized egg. After its preservation, we initiated dasatinib as her first-line-treatment. She achieved CHR in a month, CCyR in 3 months, and MMR in 10 months. Therefore, her clinical course could be evaluated as optimal. However, she strongly requested to have a baby early. We switched her TKI from dasatinib to nilotinib for deeper molecular response. 5 months later, she accidentally became pregnant. She stopped taking nilotinib at 5th week of her pregnancy and selected to give a birth even with a risk: her disease had not reached DMR. Considering her disease status, it was impossible to stop all the treatment, so we initiated IFN-alpha, which was known not to cross the placenta. She did not experience any adverse event with it, and successfully gave birth to a 2500g baby without any abnormality. We checked MRD once in 3 months, her disease kept MR4.0 all the pregnancy period.[Discussion] Discontinuation of TKIs is under trial now. According to the JSH guideline, significant treatment duration (over 3 years) and DMR
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.020/5583080 by Stockholm University Library user on 14 October 2019
Study Pharmacokinetic Behavior of MTX-HD and Rescue with Leucovorine in Human Plasma LC and RMNC13, Children Hospital
Annals of Oncology
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Guillermo O. Rocabado Calizaya, Astrid S. Riveros, Almazan Leyton Omar Department of Onco Hematology, Children’s Hospital "Dr. Ovidio Aliaga Uria", La PazBolivia, Bolivia, Plurinational State of Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in the pediatric age, treated efficiently and in cases of low risk it is possible to obtain a cure of up to 80%. However, some low-risk patients die from complications secondary to drug toxicity. In Bolivia, administering MTX at high doses represents a risk of intoxication because serum levels of the drug can not be determined for the corresponding rescue, so the optimal doses should be reduced in these high-risk patients. Equipment: Methotrexate MTX lyophilized powder. LVO leucovorin. TEAMS RMN, Bruker AVANCE AV-500 CHROMATOGRAPH HPLC, Waters: Alliance, with UV detector. Population in Study: 10 children, eight male and two female, selected at random from a targeted population. Methodology: Plasma of whole blood was used. The isocratic separation was implemented a K-C18 column (kromasil) with a mobile phase consisting of buffer of 50 mM sodium acetate (pH 3.6), acetonitrile (89:11, v / v). Results and Conclusions: High doses of MTX, start from 2000 mg to 8000 mg, children should receive the correct rescue with LVO, in this work it was shown that the concentrations prove to be inappropriate, since the start of the rescue with 0.0021 ng / ml of LVO, coincides with the highest dose of MTX of 0.16679344 ng / ml. The follow-up of the patients showed that the therapy was concluded as follows: mucositis grade 2 to 3, between days 5 and 7 after the rescues with LVO ended, this shows that the rescue and recovery should be delayed for at least 3 to 5 hours. to readjust the dose of LVO to finish with a higher dose to decrease the toxic effect of MTX. Analysis by Nuclear Magnetic Resonance: The LC signal overlaps in the sample could lead to doubt regarding a masking of the LVO peak by MTX or metabolites that have retention times between 11 and 14 minutes, which is why it was decided to apply the chemical technique of NMR-C13 which rules out the interference hypothesis.
P1
104
Targeting of versican, a proteoglycan in bone marrow microenvironment by microRNAs inhibit multiple myeloma progression
Nidhi Gupta1, Raman Kumar1, Tulika Seth2, Bhavuk Garg3, Alpana Sharma1 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India, 2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India, 3 Department of Orthopedics, All India Institute of Medical Sciences, New Delhi, India
1
Background: The abnormal growth of malignant plasma cells in Multiple myeloma (MM) require bone marrow (BM) niche consisting of proteoglycans, cytokines, etc. for their growth. One of the chondroitin sulfate proteoglycan, Versican (VCAN) has gained consideration in milieu of solid tumors but there is dearth of literature in MM. Hence, involvement of VCAN in MM and its regulation by microRNAs has been studied. Materials and Methods: 30 MM patients & 20 controls were recruited and BM Stromal Cells (BMSCs) were harvested by primary culture. Molecular expression of VCAN and microRNAs (miR-144, miR-199 & miR-203) were examined in study subjects and MM cell lines (RPMI8226 & U266). The involvement of VCAN in myeloma pathogenesis was studied using BMSCs conditioned medium (BMSCs-CM) and VCAN-neutralizing antibody or microRNA mimics (miR-144 and miR-199). Further, signaling pathways altered by knockdown of VCAN by antibody or microRNA mimics were identified. Results: Elevated expression of VCAN was found in MM patients especially in the stroma of BM niche while microRNA expression was lower in patients and showed negative correlation with VCAN levels. VCAN being produced in stroma found at lower levels in MM cell lines. Moreover, BMSCs CM showed presence of VCAN which upon supplementing to MM cells alter parameters in favour of myeloma progression, however, this effect was neutralized by VCAN antibody or miR mimics of miR-144 and miR-199. The downstream signaling of VCAN was found to activate FAK and STAT3 which subsides by using VCAN antibody or miR mimics. Conclusion: The neutralization of oncogenic effect of BMSCs CM by VCAN blockage using antibody or miR mimics affirms its plausible role in progression of MM. These findings open up new avenues for exploring VCAN as a novel therapeutic target and microRNAs as a mean to target VCAN which could be exploited in clinical settings in future.
vi122 | Poster Session
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105
Multiple Myeloma in Patient with Co-existing Chronic Renal Failure on Hemodialysis: A Case Report
Noorwati Sutandyo, Nia Novianti Hematology and Medical Oncology Department, Dharmais National Cancer Centre Hospital, Indonesia Background: Impaired renal function in multiple myeloma (MM) patients is common and will generally improve after treatment. However, some patients showed no improvement after therapy, thus, other causes of renal impairment must be suspected. Case Illustration: This is a case about a 57-year-old male MM patient with co-existing chronic renal failure due to chronic pyelonephritis and hypertension. Patients underwent routine hemodialysis twice a week and received intravenous bortezomib 1.3 mg/ m2 a day after hemodialysis, melphalan 9 mg/m2 and oral prednisone 60 mg/m2 day -1 to -4. However, there was no significant improvement in renal function. After undergoing three cycles of chemotherapy, patients experienced worsening due to sepsis, deteriorating renal function and death. Conclusion: It is a challenge to make early diagnosis and choose appropriate treatment in multiple myeloma patients with co-existing chronic renal failure. Management of MM with chronic renal failure includes supportive therapies and treatment of myeloma using the latest generation of drugs.
P1
107
Rapid improvement of secondary myelodysplastic syndrome from essential thrombocytosis (ET) treated by Azacitidine(AZA)
Masahide Yamazaki Keiju General Hospital Background: It is well known that secondary MDS is refractory to treatment. In general, high-risk MDS is treated with AZA, but its effect is often delayed. I experienced a case which has rapidly improved to the ET from secondary MDS after 2 courses of AZA. Case report: A 70 - year - old woman, who had diagnosed with ET 20 years before and treated with hydroxyurea for 5 years, was admitted to our hospital with pancytopenia. On abdominal CT, it showed splenomegaly. In chromosome testing showed complex karyotypes. Plasma WT-1 level showed a significant high as 96000 copy. In bone marrow aspiration, blasts together indicate to the atypical three strains accounted for 18%, was diagnosed with secondary MDS (RAEB-t, IPSS-R: 9.5 points). Bone marrow biopsy was similar findings and myelofibrosis was not observed. She was treated with AZA at a dose of 75 mg / m2 over a 7-day subcutaneous injection, and was followed for 3 weeks. She withdrawal from transfusion-dependent in the initial treatment, and at the time of 2 the end of the course, her WBC number (990 / ml to 7240 / ml) and Hb level (6.3 g / dl to 13.8 g / dl) were normalized, and her blood platelet count was markedly increased from 56,000 / ml to 1,340,000 / ml. Plasma WT - 1 level decreased markedly from 96000 copies to 430 copies, and the splenomegaly also improved on US study. Bone marrow aspiration showed hyperplastic bone marrow accompanied by a marked increase in megakaryocytes, the three line heterozygosity disappeared, and the blasts decreased to 1.2%. Even in bone marrow biopsy consistent with ET. Discussion: Secondary MDS developed with chemotherapy is generally often refractory to treatment. In our case, we withdrew from transfusion dependence with firsttime AZA therapy and improved to ET, the original disease at the end of 2 courses. Secondary MDS patients who respond with small number of AZA therapy are extremely rare and are valuable cases.
P1
108
An unexpected but successful pregnancy for young lady with CML
Hirofumi Yokota, Yuichiro Inagaki, Yuki Takeuchi, Shihomi Kuwano, Hitomi Sawa, Kanae Imai, Tomonori Kato, Masashi Sawa Anjo Kosei Hospital Background: The prognosis of CML has dramatically improved with the introduction of imatinib. Patients diagnosed in chronic phase can live almost as long time as healthy people. However, adequate strategy of pregnancy under TKI treatment has not been established. Case report: 31-year-old-female was introduced to us because of leukocytosis. She was diagnosed as CML CP. We let her visit OB-GYN clinic with her partner to preserve a fertilized egg. After its preservation, we initiated dasatinib as her first-line-treatment. She achieved CHR in a month, CCyR in 3 months, and MMR in 10 months. Therefore, her clinical course could be evaluated as optimal. However, she strongly requested to have a baby early. We switched her TKI from dasatinib to nilotinib for deeper molecular response. 5 months later, she accidentally became pregnant. She stopped taking nilotinib at 5th week of her pregnancy and selected to give a birth even with a risk: her disease had not reached DMR. Considering her disease status, it was impossible to stop all the treatment, so we initiated IFN-alpha, which was known not to cross the placenta. She did not experience any adverse event with it, and successfully gave birth to a 2500g baby without any abnormality. We checked MRD once in 3 months, her disease kept MR4.0 all the pregnancy period.[Discussion] Discontinuation of TKIs is under trial now. According to the JSH guideline, significant treatment duration (over 3 years) and DMR
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.020/5583080 by Stockholm University Library user on 14 October 2019
Study Pharmacokinetic Behavior of MTX-HD and Rescue with Leucovorine in Human Plasma LC and RMNC13, Children Hospital
Annals of Oncology