Treatment Pattern and Outcome of Newly Diagnosed Multiple Myeloma Patients in a Resource-Limited Setting.

BACKGROUND: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting. METHODS: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients' demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS). RESULTS: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation.  The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS. CONCLUSION: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.

CMV Infection Post Allogeneic Hematopoietic Stem Cell Transplantation in a Resource Limited Country.

Cytomegalovirus (CMV) infection is one of the common complications which can lead to significant morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). As the seroprevalence of CMV infection in Malaysia is high, this study aims to determine the prevalence of CMV infection in patients post HSCT and to evaluate the associated risk factors. Patients who underwent allogeneic HSCT in adult ward from 2008 to 2020 at a tertiary teaching hospital in Kuala Lumpur, Malaysia were studied retrospectively. They were followed up for a minimum of 100 days post-HSCT to determine the incidence of CMV infection. CMV infection was defined according to CMV Drug Development Forum 2014. Risk factors such as type of transplant, serostatus of donor and patients, age, gender, race, presence of graft versus host disease (GVHD) and underlying disease were included for analysis. A total of 112 patients were included. Forty (35.7%) patients had CMV infection with median of onset recorded as 40 days (range 13-95 days). Only haplo-identical HSCT and presence of GVHD were identified as significant risk factors. Patients who had CMV infection had a lower median survival time although this was not statistically significant. The CMV infection rate was comparable with previous reports in Asia and as expected, higher than the western countries. Therefore, vigilant monitoring of CMV infection should be implemented especially in patients who had haplo-identical HSCT and acute GVHD.

Timing advances of commercial divalent-ion co-doped LYSO:Ce and SiPMs in sub-100 ps time-of-flight positron emission tomography.

Objective.Together with novel photodetector technologies and emerging electronic front-end designs, scintillator material research is one of the key aspects to obtain ultra-fast timing in time-of-flight positron emission tomography (TOF-PET). In the late 1990s, Cerium-doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) has been established as the state-of-the-art PET scintillator due to its fast decay time, high light yield and high stopping power. It has been shown that co-doping with divalent ions, such as Ca2+and Mg2+, is beneficial for its scintillation characteristics and timing performance. Therefore, this work aims to identify a fast scintillation material to combine it with novel photosensor technologies to push the state of the art in TOF-PET.Approach.This study evaluates commercially available LYSO:Ce,Ca and LYSO:Ce,Mg samples manufactured by Taiwan Applied Crystal Co., LTD regarding their rise and decay times as well as their coincidence time resolution (CTR) with both ultra-fast high-frequency (HF) readout and commercially available readout electronics, i.e. the TOFPET2 ASIC.Main results.The co-doped samples exhibit state-of-the-art rise times of on average 60 ps and effective decay times of on average 35 ns. Using the latest technological improvements made on NUV-MT SiPMs by Fondazione Bruno Kessler and Broadcom Inc., a 3 × 3 × 19 mm3LYSO:Ce,Ca crystal achieves a CTR of 95 ps (FWHM) with ultra-fast HF readout and 157 ps (FWHM) with the system-applicable TOFPET2 ASIC. Evaluating the timing limits of the scintillation material, we even show a CTR of 56 ps (FWHM) for small 2 × 2 × 3 mm3pixels. A complete overview of the timing performance obtained with different coatings (Teflon, BaSO4) and different crystal sizes coupled to standard Broadcom AFBR-S4N33C013 SiPMs will be presented and discussed.Significance.This work thoroughly evaluates commercially available co-doped LYSO:Ce crystals and, in combination with novel NUV-MT SiPMs, shows a TOF performance that significantly exceeds the current state of the art.

SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression.

Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.

Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients.

BACKGROUND: The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. MATERIALS AND METHODS: The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. RESULTS: A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). CONCLUSIONS: The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

Acquired Factor VIII Inhibitors: Three Cases.

UNLABELLED: Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients' ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time) to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed. CONFLICT OF INTEREST: None declared.

Myeloid sarcoma: an unusual presentation of acute promyelocytic leukemia causing spinal cord compression.

Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted.