Searches / Hematology/oncology And Stem Cell Therapy[JOURNAL]

Hematology/oncology And Stem Cell Therapy[JOURNAL]

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Changes in Heme Levels During Acute Vaso-occlusive Crisis in Sickle Cell Anemia.

Cardoso EC, Silva-Neto PV, Hounkpe BW … +9 more , Chenou F, Albuquerque CCMX, Garcia NP, Silva-Junior AL, Malheiro A, Cesar P, de Lima F, De Paula EV, Fraiji NA

Hematol Oncol Stem Cell Ther · 2023 Jan · PMID 34450106 · Publisher ↗

OBJECTIVE/BACKGROUND: Sickle cell anemia (SCA) is associated with increased levels of extracellular heme, which is a key mediator of inflammation in this condition. Despite abundant evidence supporting this concept in ce... OBJECTIVE/BACKGROUND: Sickle cell anemia (SCA) is associated with increased levels of extracellular heme, which is a key mediator of inflammation in this condition. Despite abundant evidence supporting this concept in cell and animal models, few studies addressed the association between heme levels and the development and severity of acute vasoocclusive crises (VOC) in humans. METHODS: A cross-sectional study was conducted in patients with acute VOC. Total extracellular heme levels were measured in both plasma and serum at admission and after convalescence, and correlated with other clinical and laboratory markers of SCA severity. RESULTS: A total of 28 episodes of VOC in 25 patients were included. Heme levels were similar between admission and convalescence, and correlated with the difference between pre and post hemoglobin, and SCA severity estimated by a composite score of clinical and laboratory markers. Heme levels were neither associated with VOC severity nor with markers of hemostasis activation, and were similar to those reported in an independent population of SCA patients at steady state. DISCUSSION: Acute VOC are not characterized by significant increases in total extracellular heme levels. Studies measuring the fraction of free extracellular heme unbound to proteins are warranted to further refine our understanding of the role of heme in acute VOC.

Impact of Pre-transplant Induction Therapy on Outcomes of Patients Who Undergo Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in First Complete Remission.

Albanyan O, Alkassis S, Kim S … +7 more , Kin A, Alavi A, Ayash L, Ratanatharathorn V, Modi D, Uberti JP, Deol A

Hematol Oncol Stem Cell Ther · 2023 Jan · PMID 34425096 · Publisher ↗

Mantle cell lymphoma is a rare subtype of non-Hodgkin's lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical t... Mantle cell lymphoma is a rare subtype of non-Hodgkin's lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical trials. We retrospectively evaluated 66 patients diagnosed with mantle cell lymphoma who achieved first complete response after induction chemotherapy followed by autologous stem cell transplant. Treatment groups were divided into low-intensity versus high-intensity regimens. Our data showed the intensity of induction regimen does not impact posttransplant outcomes of mantle cell lymphoma who underwent autologous stem cell transplant in first complete response.

High expression of long noncoding RNA NORAD is associated with poor clinical outcomes in non-M3 acute myeloid leukemia patients.

Masoud Eslami M, Soufizomorrod M, Ahmadvand M

Hematol Oncol Stem Cell Ther · 2021 Aug · PMID 34419481 · Publisher ↗

OBJECTIVE/BACKGROUND: Dysregulation of long noncoding RNA NORAD has been identified in human solid tumors. However, the expression profile of NORAD and its clinical implications in acute myeloid leukemia (AML) is unclear... OBJECTIVE/BACKGROUND: Dysregulation of long noncoding RNA NORAD has been identified in human solid tumors. However, the expression profile of NORAD and its clinical implications in acute myeloid leukemia (AML) is unclear. The current study aimed to explore the NORAD expression status and its clinical significance in non-M3 AML patients. METHODS: NORAD expression was evaluated in 60 de novo non-M3 AML patients and 49 healthy individuals using quantitative reverse transcription-polymerase chain reaction method. The correlation between NORAD transcription levels and clinicopathologic characteristics was statistically studied. RESULTS: Compared with the healthy controls, NORAD was consistently higher in non-M3 AML patients (p = .01). Furthermore, initial NORAD upregulation occurred more frequently in patients with unfavorable cytogenetic risk (p = .02). The non-M3 AML patients were divided into NORAD high-expressing (NORAD) and NORAD low-expressing (NORAD) groups based on the median NORAD expression level. Univariate analyses revealed that patients with high expression levels of NORAD had relatively poor overall survival (p = .03) and relapse-free survival (RFS) (p = .01). Additionally, multivariate analysis highlighted that NORAD upregulation was an independent risk factor for RFS. CONCLUSION: Our observations indicate the fact that high expression of NORAD could be an unfavorable risk factor in non-M3 AML patients, and NORAD might be a novel therapeutic candidate for future treatments targeting AML.

Effect of Ibrutinib on Hmphocytic Leukemia: a Single-Center Experience.

Hassan H, Ammad Ud Din M, Jamshed S … +2 more , Bress J, Mustafa SS

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34391729 · Publisher ↗

OBJECTIVE/BACKGROUND: In the era of novel agents, Bruton tyrosine kinase (BTK) inhibitors have changed the dynamics of treating chronic lymphocytic leukemia. However, small studies have shown conflicting results regardin... OBJECTIVE/BACKGROUND: In the era of novel agents, Bruton tyrosine kinase (BTK) inhibitors have changed the dynamics of treating chronic lymphocytic leukemia. However, small studies have shown conflicting results regarding the additive humoral dysfunction with their use. METHODS: We prospectively compared vaccine responses in patients on ibrutinib (n = 10) with matched controls (n = 16) and analyzed whether a protein-based (tetanus-diphtheria toxoid) or a carbohydrate (Pneumovax) moiety will result in an improved immunological response. RESULTS: An appropriate serological response in IgG titers for diphtheria was seen in 40% of patients on ibrutinib and 31% of patients in the control group. About 30% of patients on ibrutinib and 44% of patients in the control group had an adequate response to tetanus toxoid. None of the patients on ibrutinib mounted an adequate response to Pneumovax, while 31% of patients in the control arm responded appropriately. These differences in the results were considered insignificant as all p values were greater than the cut-off of 0.05. CONCLUSION: Our study did not show significant detrimental vaccine responses with ibrutinib and calls for larger multicenter studies to elucidate long-term effects, especially in patients with prior exposure to anti-CD20 monoclonal antibodies.

The Impact of Post-Hematopoietic Stem Cell Transplant Tyrosine Kinase Inhibitors in Philadelphia-Positive Acute Lymphoblastic Leukemia.

Halahleh K, Al Rimawi D, Abu Ghosh A … +3 more , Muradi I, Da'na W, Hamadani M

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34352199 · Publisher ↗

Abstract loading — click title to view on PubMed.

Cross Fire: Daratumumab-Based Therapies Are Standard of Care in Newly Diagnosed Multiple Myeloma.

Korde N, Usmani SZ

Hematol Oncol Stem Cell Ther · 2023 Jan · PMID 34343494 · Publisher ↗

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Cytogenetic Influence on Prognosis in Acute Promyelocytic Leukaemia: A Cohort Study in Vietnam.

Vu MP, Nguyen CN, Vu H

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34270998 · Publisher ↗

OBJECTIVE/BACKGROUND: To analyse the influence of chromosomal aberrations in addition to t(15;17)(q22;q21) in acute promyelocytic leukaemia (APL) on clinical characteristics and treatment outcomes. METHODS: Fifty-seven p... OBJECTIVE/BACKGROUND: To analyse the influence of chromosomal aberrations in addition to t(15;17)(q22;q21) in acute promyelocytic leukaemia (APL) on clinical characteristics and treatment outcomes. METHODS: Fifty-seven patients with new APL diagnoses underwent conventional cytogenetic analysis; fluorescence in situ hybridization for t(15;17)(q22;q21) and reverse transcriptase-polymerase chain reaction detected PML/RARα in two forms: L (length) and S (short) and accepted treatment with all-trans retinoic acid and chemotherapy. Patients with additional chromosome aberrations were designated as the complex karyotype group and were compared with patients with only t(15;17), who were designated as the simple karyotype group. RESULTS: Additional chromosome aberrations was observed in 18/57 patients (31.6%) at initial diagnosis. Outcome was significantly different between the simple karyotype group and the complex karyotype group for complete remission (92.3% vs. 66.7% respectively, p = .025), overall survival at 3 years (92.3% vs. 65.0%, respectively, p = .017), and progression-free survival at 3 years (81.4% vs. 44.4%, respectively, p = .024). CONCLUSIONS: Additional chromosome aberrations had adverse effects on the prognosis in APL.

Escalated Dose Donor Lymphocyte Infusion Treatment in Patients with Primary Immune Deficiencies After HSCT with Reduced-Intensity Conditioning Regimen.

Ali T, Behfar M, Mohseni R … +7 more , Salajegheh P, Kheder M, Abou-Fakher F, Nikfetrat Z, Jafari F, Naji P, Hamidieh AA

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34242597 · Publisher ↗

OBJECTIVE/BACKGROUND: Mixed chimerism is a major concern after allogenic hematopoietic stem cell transplantation (HSCT) using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor l... OBJECTIVE/BACKGROUND: Mixed chimerism is a major concern after allogenic hematopoietic stem cell transplantation (HSCT) using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor lymphocyte infusion (DLI) escalating dose regimen has been developed with the aim of reducing toxicity while preserving efficacy. However, the graft-versus-host disease (GvHD) development remains the most common and adverse effect of DLI and continues to be a limiting factor in its application, especially nonmalignant diseases such as PIDs. We prospectively evaluated PID patients after HSCT using RIC in Childrens Medical Center, who were candidates for an escalating dose of DLI for MC from 2016 to 2018. METHODS: With the median follow-up of 16.4 months, 12 patients (nine males and three females) with a median age of 3.72 years received DLI. The median number of DLI was 3.2 (range, 1-5), the maximum and total dose of DLIs administered per patient were 3.6 × 10 (range, 1-5) cells/kg CD3 and 9.3 × 10 (range, 1-15) cells/kg CD3 cells, respectively. RESULTS: Median donor chimerism at baseline before the DLIs was 41% (range, 11-73%), patients received DLIs at a median of 105 (range, 37-230) days and 52 (range, 3-168) days after the HSCT and onset of the MC, respectively. At the final assessment, six (54.5%) patients improved after DLIs at a median of 47.3 days. CONCLUSION: PID patients may benefit from DLI with an escalating dose regimen, but the GvHD development remains a concern during the DLI, and the optimum dose and frequency must be standardized.

The Phenomenon of Multidrug Resistance in Glioblastomas.

Chernov AN, Alaverdian DA, Galimova ES … +4 more , Renieri A, Frullanti E, Meloni I, Shamova OV

Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 34216549 · Publisher ↗

The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresi... The most common and aggressive brain tumor in the adult population is glioblastoma (GBM). The lifespan of patients does not exceed 22 months. One of the reasons for the low effectiveness of GBM treatment is its radioresistance and chemoresistance. In the current review, we discuss the phenomenon of multidrug resistance of GBM in the context of the expression of ABC family transporter proteins and the mechanisms of proliferation, angiogenesis, and recurrence. We focused on the search of molecular targets among growth factors, receptors, signal transduction proteins, microRNAs, transcription factors, proto-oncogenes, tumor suppressor genes, and their single-nucleotide polymorphisms.

Using the Appropriate Formula for QT Measurement Can Save Lives.

Al-Tweigeri T, Dent S, Al Sayed A … +5 more , Mohty D, Suleman K, Ajarim D, Raef H, Echahidi N

Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 34181897 · Publisher ↗

CDK 4/6 inhibitors, in combination with endocrine therapy, are the standard of care for patients with endocrinesensitive advanced breast cancer. This class of drug, however, is associated with QT prolongation, which serv... CDK 4/6 inhibitors, in combination with endocrine therapy, are the standard of care for patients with endocrinesensitive advanced breast cancer. This class of drug, however, is associated with QT prolongation, which serves as a surrogate marker for Torsades de Pointes (TdP), a cause of life-threatening ventricular arrhythmias and sudden cardiac death. The ICH E14 guidance document uses the Bazett formula for reporting of cardio-dynamic and safety ECG data in clinical trials. While there is substantial familiarity with the Bazett (QTcB) formula (QT/(RR) 1/2), the Fridericia (QTcF) formula (QT/(RR) 1/3 ) is preferred in the cancer population as it is often more accurate at heart rate extreme. Accordingly, the Fridericia formula is currently the standard adopted by the FDA when submitting QT data for review. At the King Faisal Specialist Hospital and Research Center, a total of 82 patients with advanced breast cancer, had a baseline ECG on day 1 before the initiation of ribociclib based therapy. Of the enrolled 82 patients, 19 (23%) were initially excluded from receiving ribociclib based due to a prolonged QTc >450ms, however, when the QTc-interval was manually measured and recalculated using Fridericia and Framingham formulae using MDCalC (https://www.mdcalc.com),17 of 19 patients successfully received their treatment without any arrhythmogenic effects. Repeat ECG on day14, and day 1 of cycle 2 demonstrated that none of these patients had QTc exceeding 480 ms. Our data highlights the complexities of evaluating the QT interval in oncology patients and the utility of the Fridericia/Framingham formulae in this population. Given these findings, we recommend the adoption of the Fridericia or Framingham formulae for measurement of QTc in all cancer patients exposed to potentially QT-prolonging cancer therapy.

Recurrence Score Testing Does not Appear to Benefit Patients With Grade 1, Progesterone Receptor-Positive Breast Cancers: An Opportunity to Eliminate Overtreatment and Decrease Testing Costs.

Sibia US, Sanders TJ, Mylander C … +4 more , Rosman M, Tweed C, Tafra L, Jackson RS

Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 34174200 · Publisher ↗

BACKGROUND: We previously described a risk prediction model (Anne Arundel Medical Center [AAMC] model) based on pathology which may eliminate the need for recurrence score (RS) testing in select early-stage breast cancer... BACKGROUND: We previously described a risk prediction model (Anne Arundel Medical Center [AAMC] model) based on pathology which may eliminate the need for recurrence score (RS) testing in select early-stage breast cancers. There is a concern that patients in discordant risk prediction groups (AAMC vs. RS) may be overtreated or undertreated if RS testing were omitted. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database for all breast cancer patients between 2004 and 2015. AAMC low-risk was defined as Grade 1 and progesterone receptor-positive (PR + ) tumors, while AAMC high-risk was defined as Grade 3 or estrogen-negative tumors. RS low-risk group was defined as RS < 16 and age ≤ 50 years, or RS ≤ 25 and age > 50 years. RS high-risk group was defined as RS > 25. RESULTS: A total of 71,212 cases were analyzed. Of these, 590 were AAMC low-risk/RS high-risk discordant, while 5,596 were AAMC high-risk/RS low-risk discordant. For AAMC low-risk/RS high-risk discordant, 10-year breast cancer-specific survival (BCSS) did not differ for patients who received adjuvant chemotherapy versus those who did not (93% chemotherapy vs. 99% unknown/no chemotherapy, p = .12). Overall survival (OS) was also comparable (92% chemotherapy vs. 91% unknown/no chemotherapy, p = .42). In the AAMC high-risk/RS low-risk discordant group, 10-year BCSS (92% chemotherapy vs. 96% unknown/no chemotherapy, p = .06) and OS (87% chemotherapy vs. 90% unknown/no chemotherapy, p = .52) did not differ between adjuvant chemotherapy and unknown/no chemotherapy groups. CONCLUSIONS: Adjuvant chemotherapy in the AAMC low-risk/RS high-risk and AAMC high-risk/RS low-risk discordant groups did not improve survival. This supports consideration of omission of RS testing in Grade 1, PR + tumors. Patients with Grade 3 tumors do benefit from RS testing.

Priapism in Lymphoproliferative Disorders: A Systematic Review.

Ali EA, Sardar S, Yassin MA

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34157311 · Publisher ↗

Priapism is defined as a persistent penile erection lasting more than 4 h. We searched the literature for reviews, case reports, and series for patients with lymphoproliferative disorders who developed priapism. The sear... Priapism is defined as a persistent penile erection lasting more than 4 h. We searched the literature for reviews, case reports, and series for patients with lymphoproliferative disorders who developed priapism. The search involved all the lymphoproliferative disorders included in the revised 2016 World Health Organization classification of lymphoid neoplasms including chronic lymphocytic leukemia, multiple myeloma, Waldenström macroglobulinemia, and lymphomas. A total of 16 articles were found. The search included cases up to 4 January 2021. Priapism was seen most commonly as the first manifestation of lymphoproliferative disorders, rarely seen after treatment or after diagnosis.

Use of Thrombopoietin Receptor Agonists in Pregnancy: A Review of the Literature.

Howaidi J, AlRajhi AM, Howaidi A … +2 more , AlNajjar FH, Tailor IK

Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 34153229 · Publisher ↗

The management of immune thrombocytopenic purpura (ITP) involves several lines of therapy such as corticosteroids and intravenous immunoglobulin. With the emergence of novel therapies such as thrombopoietin receptor agon... The management of immune thrombocytopenic purpura (ITP) involves several lines of therapy such as corticosteroids and intravenous immunoglobulin. With the emergence of novel therapies such as thrombopoietin receptor agonists (TPO-RAs), there has been a shift in treatment modalities. Eltrombopag and romiplostim have proven to be effective in the management of ITP through clinical studies, but their safety in pregnancy remains uncertain. The purpose of the study is to review the literature to evaluate the safety of TPO-RAs in pregnant women. Ten case reports and a cohort study pertaining to the use of TPO-RAs in pregnancy were obtained. According to the reported cases and prospective study, the use of eltrombopag and romiplostim appears to be relatively safe in the first, second, and third trimesters, as there were no reported congenital malformations. Low fetal birth weight has been observed following the administration of eltrombopag during the second trimester, whereas preterm birth has occurred following the administration of eltrombopag in the third trimester. Eltrombopag and romiplostim seem relatively safe. Further studies are necessary to clarify their safety during pregnancy.

Primary Mediastinal Large B-cell Lymphoma : Impact of Chemotherapy Choice.

Elhagracy R, Hamadah A, Abd El Tawab R … +4 more , Pinto K, Hussain A, Osmani M, Alshemmari S

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 34118210 · Publisher ↗

OBJECTIVE/BACKGROUND: Data generated from retrospective studies on primary mediastinal B-cell lymphoma (PMBCL) outcome are valuable as no prospective phase 3 trials have been conducted in this rare type of lymphoma. METH... OBJECTIVE/BACKGROUND: Data generated from retrospective studies on primary mediastinal B-cell lymphoma (PMBCL) outcome are valuable as no prospective phase 3 trials have been conducted in this rare type of lymphoma. METHODS: Our goal was to assess the long-term outcome of 41 patients with PMBCL who were treated at the Kuwait Cancer Center. We evaluated two types of multidrug treatment, R-CHOP (rituximab, vincristine, doxorubicin, cyclophosphamide, and prednisone) and DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), and determined overall survival and complete response (CR) as primary endpoints. RESULTS: In our cohort, 27 (66%) cases were treated with R-CHOP and 14 (34%) cases were treated with DA-EPOCH-R. The overall median follow-up time was 34 months. Among the patients treated with R-CHOP, 23 out of 27 (92.6%) patients achieved CR; similarly, 10 out of 14 patients (85.7%) in the DA-EPOCH-R group achieved CR after initial treatment. There were no differences in OS between patients treated with R-CHOP versus DA-EPOCH-R. CONCLUSION: The findings of this study indicate that combined chemotherapy and immunotherapy results in excellent long-term outcome of patients with PMBCL. At our center, we prefer R-CHOP to DA-EPOCH-R for low-risk patients with nonbulky disease.

Diagnosis and Treatment of Subcutaneous Panniculitis-like T-cell Lymphoma: A Systematic Literature Review.

Alsomali DY, Bakshi N, Kharfan-Dabaja M … +2 more , El Fakih R, Aljurf M

Hematol Oncol Stem Cell Ther · 2023 Jan · PMID 34015273 · Publisher ↗

OBJECTIVES: The aim of this systematic review is to investigate different diagnostic methods and the available treatment options for subcutaneous panniculitis-like T-cell lymphoma (SPTCL). METHODS: We searched PubMed, We... OBJECTIVES: The aim of this systematic review is to investigate different diagnostic methods and the available treatment options for subcutaneous panniculitis-like T-cell lymphoma (SPTCL). METHODS: We searched PubMed, Web of Science, SCOPUS, EBSCO, and CINAHL Plus for published case reports of SPTCL. From each record, we extracted data of the diagnostic methods, immunohistochemical profile, clinical characteristics, and the treatment approaches provided. Data were summarized and narratively synthesized to highlight the various diagnostic methods and treatment options of SPTCL. RESULTS: Our literature search yielded 1293 unique citations. Following screening, nine articles reporting a total of 15 cases were included in this systematic review. All patients presented with subcutaneous nodules. Three of the 15 cases were initially misdiagnosed. The atypical lymphoid cells were positive for CD2, CD3, granzyme B, and TIA-1 and negative for CD1a, EBER, and CD20 in all the reported cases. The atypical lymphoid cells were positive for CD45RO in four out of seven cases, positive for CD56 in three out of 12 cases tested, while positive for CD5 and CD8 in the majority of cases. Therapy ranged from topical agents to immunosuppressive agents all the way to multiagent chemotherapy. CONCLUSION: SPTCL is a rare lymphoma. Diagnosis is highly dependent on the immunohistochemical stains added to histopathologic and radiologic findings. Therapy is dependent on the pace of the disease, with encouraging results obtained with single-agent cyclosporine.

Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens in Patients with Lymphoma.

Gunes AK, Serin I, Demir I … +7 more , Sarifakiogullari S, Durusoy SS, Akkurt DM, Ince I, Ozkan G, Cinli TA, Pehlivan M

Hematol Oncol Stem Cell Ther · 2022 Dec · PMID 33933474 · Publisher ↗

OBJECTIVE/BACKGROUND: Lymphoma is seen as a highly treatable and curable malignancy with aggressive treatment methods. Efficacy is often limited by toxicity and many patients need alternative treatment strategies as they... OBJECTIVE/BACKGROUND: Lymphoma is seen as a highly treatable and curable malignancy with aggressive treatment methods. Efficacy is often limited by toxicity and many patients need alternative treatment strategies as they cannot tolerate existing high cytotoxic approaches. Our aim is to compare BEAM [carmustine (BCNU), etoposide, cytarabine (ARA-C, cytosine arabinoside), and melphalan] and mitoxantrone-melphalan (Mx-Mel) regimens utilized in our patients with a diagnosis of lymphoma who underwent autologous stem cell transplantation (ASCT), and to demonstrate that the Mx-Mel regimen has similar but less toxic results than the BEAM regimen we have been using frequently as standard conditioning regimen. METHODS: A total of 101 patients with lymphoma who underwent ASCT were included in our study. The BEAM regimen included BCNU, etoposide, ARA-C, and melphalan. The Mx-Mel regimen included mitoxantrone and melphalan. RESULTS: Of 101 patients included in the study, 60 (59.4%) received BEAM and 41 (40.6%) received Mx-Mel (40.6%) conditioning regimen. The median time to neutrophil engraftment was 10 (range: 9-20) days and 12 (range: 9-12) days in the BEAM and Mx-Mel arms, respectively; it was statistically significantly shorter in the BEAM arm (p = .001). CONCLUSION: This study demonstrates that the Mx-Mel regimen has similar efficacy and toxicity compared with the BEAM regimen. Although time to neutrophil engraftment was shorter in the BEAM arm, it did not result as significant transplant-related complications between the two regimens. The Mx-Mel regimen is seen as a good alternative with low toxicity and high efficacy.

Mutation Profile in BCR-ABL1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India.

Maddali M, Kulkarni UP, Ravindra N … +12 more , Arunachalam AK, Venkatraman A, Lionel S, Manipadam MT, Devasia AJ, Korula A, Fouzia NA, Abraham A, Srivastava A, George B, Balasubramanian P, Mathews V

Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 33789164 · Full text

OBJECTIVE/BACKGROUND: Recurrent somatic mutations in the JAK2, calreticulin (CALR), and the MPL genes are described as drivers of BCR-ABL1-negative myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV),... OBJECTIVE/BACKGROUND: Recurrent somatic mutations in the JAK2, calreticulin (CALR), and the MPL genes are described as drivers of BCR-ABL1-negative myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and MPN unclassified (MPN-U). METHODS: We describe the mutation profile and clinical features of MPN cases diagnosed at a tertiary care center. JAK2V617F and MPL (S505/W515) mutations were screened by allele-specific polymerase chain reaction, while CALR exon 9 and JAK2 exon 12 mutations were screened by fragment analysis/Sanger sequencing. Among the 1,570 patients tested for these mutations during the study period, 407 were classified as MPN with a diagnosis of PV, ET, PMF, and MPN-U seen in 30%, 17%, 36%, and 17%, respectively, screened. RESULTS: Similar to previous reports from Asian countries, the incidence of PMF was the highest among the classic MPN. JAK2V617F mutation was detected in 90% of PV, 38% of ET, 48% of PMF, and 65% of MPN-U. JAK2 exon 12 mutations were seen in 5.7% of PV and 1.4% of PMF. CALR exon 9 mutations were seen in 33% of ET, 33% of PMF, and 12% of MPN-U. MPL mutations were detected in 2.8%, 2.7%, and 2.9% of ET, PMF, and MPN-U, respectively. Fifteen % of PMF, 26% of ET, and 22% of MPN-U were triple negative. CONCLUSION: There was a significantly higher incidence of CALR mutation in PMF and ET cases. Our study highlights the challenges in the diagnosis of JAK2-negative PV and the need for harmonization of criteria for the same.

Efficacy of Allogeneic Hematopoietic Cell Transplantation in Patients With Chronic Phase CML Resistant or Intolerant to Tyrosine Kinase Inhibitors.

Yassine F, Reljic T, Moustafa MA … +4 more , Iqbal M, Murthy HS, Kumar A, Kharfan-Dabaja MA

Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 33789163 · Publisher ↗

Approximately 15-20% of chronic myeloid leukemia (CML) patients fail tyrosine kinase inhibitor (TKI) therapy secondary to resistance or intolerance. In the pre-TKI era, front-line allogeneic hematopoietic cell transplant... Approximately 15-20% of chronic myeloid leukemia (CML) patients fail tyrosine kinase inhibitor (TKI) therapy secondary to resistance or intolerance. In the pre-TKI era, front-line allogeneic hematopoietic cell transplantation (allo- HCT) represented the standard approach for patients with chronic phase-CML (CP-CML) who were deemed fit to tolerate the procedure and had a human leukocyte antigen compatible donor available. Currently, CP-CML patients are eligible for allo-HCT only if they fail more than one TKI and/or are intolerant to the drug. We performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease), and stratified by age into adult and pediatric groups. For adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84% [95% confidence interval (CI) 59-99%], 66% (95% CI 59-73%), 56% (95% CI 30-80%), and 88% (95% CI 62-98%), respectively. Pooled NRM and relapse were 20% (95% CI 15-26%) and 19% (95% CI 10-28%), respectively. For the pediatric group, the OS rate was reported in one study and was 91% (95% CI 72-99%). Our results suggest that allo-HCT is an effective treatment for TKI-resistant or TKI-intolerant CP-CML. Post-transplant strategies are still needed to further mitigate the risk of relapse.

Microbiota phylogenic analysis revealed decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal bacterium, in patients with chronic graft-versus-host disease.

Farhadfar N, Gharaibeh RZ, Lyon D … +7 more , Whitlock JA, Murthy HS, Weaver MT, Wang GP, Jobin C, Wingard JR, Kelly DL

Hematol Oncol Stem Cell Ther · 2021 Sep · PMID 33785388 · Publisher ↗

Abstract loading — click title to view on PubMed.

Predictors of Outcomes of Therapy-Related Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Nampoothiri RV, Law AD, Lam W … +9 more , Chen C, Al-Shaibani Z, Loach D, Michelis FV, Kim DDH, Mattsson J, Kumar R, Lipton JH, Viswabandya A

Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 33775624 · Publisher ↗

BACKGROUND/OBJECTIVE: Existing literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML... BACKGROUND/OBJECTIVE: Existing literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML and t-MDS. We aim to report our 20-year experience of HSCT in t-AML. METHODS: We retrospectively reviewed patients with t-AML who underwent HSCT. Patients were analyzed for prior malignancy, therapy, time to diagnosis of t-AML, transplant details, relapse-free survival (RFS), overall survival (OS), and predictors of outcomes. RESULTS: In total, 68 patients (59.9% female; median age, 56.5 years) underwent HSCT. Acute and chronic graft-versus-host disease (GVHD) occurred in 39 (57.4%) and 23 (33.8%) patients, respectively. Cumulative incidence of relapse, nonrelapse mortality, RFS, and OS at 2 years were 17.9%, 34.5%, 47.6%, and 49.3%, respectively. Significant predictors of reduced OS were presence of 11q23 rearrangement (hazard ratio [HR], 3.24), using induction regimens other than FLAGI-da or 7 + 3 (HR, 3.65), haploidentical donors (HR, 3.48), Eastern Cooperative Oncology Group performance status 2 or higher (HR, 5.83), and using cyclosporine A-methotrexate as GVHD prophylaxis (HR, 2.41). A significant decrement in survival was seen with an increasing number of any of these prognostic factors. CONCLUSION: Outcomes of t-AML are satisfactory after allo-HSCT. Patients with t-AML with good-risk karyotypes, good performance status, having HLA-matched donors, and receiving intensive induction regimens have better outcomes after HSCT.
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