Identification of warning signs in Malaysian patients having COVID-19 infection who progress to severe form of the illness.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus, now widely known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused 3 major pandemic waves in Malaysia. We aimed to identify the warning signs as indicators that predict the progression of disease. MATERIALS AND METHODS: This is a retrospective cohort study of adult patients more than 12 years of age presenting with laboratory-confirmed COVID-19 admitted in three separate hospitals around the country. RESULTS: Of the 228 patients initially admitted with mild illness, 47 had progressed requiring oxygen. The median time from admission to deterioration was 3 days (IQR 2 - 5). Age more than ≥50years old (median age = 42.5, IQR = 28.8 - 57.0), higher temperature (mean = 37.3, IQR 36.8 - 38.0), MEWS score >3 (9, 19.1%), Neutrophil-to-lymphocyte ratio (NLR) >3.13 , (18, 38.3%) C-reactive protein (CRP) >5. (12, 27.3%), multiple zonal involvement on the chest radiography on admission (2, IQR 1-3) were more common in the deteriorated group on admission. On multivariate analysis, multiple comorbidities (HR = 7.40, 95 percent CI 2.58-21.2, p0.001), presence of persistent fever (HR = 2.88, 95 percent CI 1.15 - 7.2, p = 0.024), MEWS scoring >3 (HR of 6.72 ;95 percent CI 2.81-16.0, p0.001) were associated with progression to severe illness. CONCLUSION: In our cohort, we found that several factors were associated with the severity of COVID19. Early detection of these factors could correctly identify patients who need more intensive monitoring, and early referral for ICU care.

Diagnostic significance of serum miR-26b and miR-21 expressions in ovarian cancer and their associations with clinicopathological characteristics and prognosis of patients.

OBJECTIVE: The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. PATIENTS AND METHODS: A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. RESULTS: The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. CONCLUSIONS: MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Superconducting and normal-state anisotropy of the doped topological insulator Sr0.1Bi2Se3.

SrxBi2Se3 and the related compounds CuxBi2Se3 and NbxBi2Se3 have attracted considerable interest, as these materials may be realizations of unconventional topological superconductors. Superconductivity with Tc ~3 K in SrxBi2Se3 arises upon intercalation of Sr into the layered topological insulator Bi2Se3. Here we elucidate the anisotropy of the normal and superconducting state of Sr0.1Bi2Se3 with angular dependent magnetotransport and thermodynamic measurements. High resolution x-ray diffraction studies underline the high crystalline quality of the samples. We demonstrate that the normal state electronic and magnetic properties of Sr0.1Bi2Se3 are isotropic in the basal plane while we observe a large two-fold in-plane anisotropy of the upper critical field in the superconducting state. Our results support the recently proposed odd-parity nematic state characterized by a nodal gap of Eu symmetry in SrxBi2Se3.

HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era.

Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R) at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL) <50 copies/mL. Patients received PCP prophylaxis and G-CSF, 13 received HAART with chemotherapy and 10 rituximab. There were 63 episodes of toxicity, none fatal, including: bacterial infection, n = 20; grade 3-4 hematologic toxicity, n = 14; febrile neutropenia, n = 7; oral thrush; and ifosfamide neurological toxicity, n = 1 each. At a median followup of 11.7 months, 12 (86%) patients are alive and in remission. All 10 patients who received HAART, chemotherapy, and rituximab are alive. CD4 counts and HIV VL 6 months following BL therapy completion (n = 5 patients) were >250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

Loading behavior of Pt nanoparticles on the surface of multiwalled carbon nanotubes having defects formed via microwave treatment.

We developed a simple and efficient method to load Pt nanoparticles (NPs) uniformly on defects generated in multiwalled CNTs (MWCNTs) without using reduction agents or organic reagents. Defects on the surfaces of MWCNTs were artificially generated by microwave treatment at various exposure times. Nucleation of Pt NPs occurs on the defect sites spontaneously due to an innate electropotential difference. Because of the correlation between defects and Pt NPs, we were able to control the size of Pt NPs by changing defect size, quantity and distribution, which was confirmed by Raman spectroscopy and TEM. After microwave treatment for 3 min, more uniform and smaller Pt NPs were observed. Also, the defects via microwave treatment make adhesion of Pt NPs stronger, which can be helpful to improve the reliability for applications. Finally, the methanol oxidation behavior of MWCNTs with Pt NPs was examined by cyclic voltammetry (CV).

Comparison of the molecular adsorbent recirculating system and plasmapheresis for patients with graft dysfunction after liver transplantation.

BACKGROUND: Graft dysfunction after liver transplantation (OLT) is a life- threatening condition. Molecular adsorbent recirculating system (MARS) or plasmapheresis (PLP) may be effective supportive therapy of graft dysfunction for patients who cannot undergo retransplantation. The aim of this study was to compare the effects of MARS and PLP in patients with graft dysfunction after OLT. METHODS: Between January 2002 and July 2007, 31 OLT recipients who experienced graft dysfunction, defined as hyperbilirubinemia (>10 mg/dL) without bile duct obstruction and/or presence of hepatic encephalopathy, were treated with MARS or PLP. Biochemical and hemodynamic data and survival were compared in MARS and PLP groups. RESULTS: Fifteen patients were treated with 41 MARS sessions and 16 with 105 PLP sessions. After a single MARS session, patients showed significant reductions in creatinine, urea nitrogen, bilirubin, and ammonia. After a single PLP session, patients showed significant improvements in prothrombin time, bilirubin, alanine aminotransferase, alkaline phosphatase, and albumin. After the completion of treatment, Both MARS and PLP significantly improved bilirubin values. at 90 days there were no differences in overall survival rates; 53% in MARS versus 56% in PLP. CONCLUSION: Both MARS and PLP are alternative supportive treatments for graft dysfunction after OLT.

Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens.

We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for > or =2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of non-relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.

Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML.

Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.

Allogeneic SCT for relapsed composite and transformed lymphoma using related and unrelated donors: long-term results.

Outcome is poor with conventional therapy for relapsed transformed non-Hodgkin's lymphoma (NHL). Autologous SCT has been successfully employed; however the impact of allogeneic SCT has not been well defined. We therefore studied 40 consecutive patients who received allogeneic SCT for relapsed composite and transformed NHL (25 transformed, 8 composite (same site) and 7 discordant (different sites)) with related (n=25) and unrelated donors (n=15) to evaluate long-term outcome. Conditioning was myeloablative in the majority (39 of 40). Of 40 patients, 11 survive with median follow-up of 25 months. Death occurred in similar proportions due to relapsed NHL (n=14) or treatment-related complications (transplant-related mortality, TRM; n=15). The cumulative incidence of TRM was 36% at 3 years and disease relapse was 42% at 5 years. Probability of 2- and 5-year event-free survival is 36 and 23% with overall survival 39 and 23%. Performance of SCT within 1 year of NHL diagnosis predicted improved outcome. Relapse and TRM remain significant problems in this setting, indicating the need for strategies whereby patients at high risk of transformation should be selected for early SCT, ideally before their actual transformation.

Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia.

BACKGROUND: Curative intent chemotherapy for acute myelogenous leukemia (AML) leads to prolonged severe neutropenia, during which patients are highly susceptible to infection. Traditionally these high-risk patients were treated as inpatients. Our center recently implemented a selective ambulatory management policy for AML patients undergoing chemotherapy. MATERIALS AND METHODS: A retrospective analysis was conducted to assess the occurrence of septicemia in AML patients treated over a 5 years period with curative intent chemotherapy. This review encompasses a change in policy from primarily inpatient care to selective outpatient management coupled with prophylactic antibiotic therapy. RESULTS: A total of 294 patients, receiving 623 cycles of chemotherapy were identified. A significant decrease in septicemia was observed from the inpatient to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift towards outpatient treatment of consolidation cycles. A shift from Gram-negative to Gram-positive organisms as the cause of septicemia was also detected in the outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis. No significant emerging resistance and no septicemia-related mortality were noted in the outpatient cohort. CONCLUSION: The observed decrease in the incidence of septicemia in the ambulatory cohort adds supportive evidence to the feasibility of selective outpatient management of AML patients with respect to infectious complications.

Primary therapy for adults with T-cell lymphoblastic lymphoma with hematopoietic stem-cell transplantation results in favorable outcomes.

BACKGROUND: Controversy exists regarding the role of high-dose therapy followed by stem-cell transplant (SCT) in the treatment of T-cell lymphoblastic lymphoma (T-LBL). We conducted an intention-to-treat analysis of the strategy of SCT as definitive treatment of T-LBL. PATIENTS AND METHODS: From July 1987 to March 2005, 34 adults with T-LBL were diagnosed and treated in British Columbia. Treatment, before planned SCT, consisted of a non-Hodgkin's lymphoma (NHL)/acute lymphoblastic leukemia hybrid chemotherapy protocol (28 patients) or a standard NHL chemotherapy regimen (six patients). RESULTS: Median follow-up of the 23 surviving patients is 51 months (range 13-142 months). Twenty-nine proceeded to SCT (four allogeneic, 25 autologous). For all 34 patients, 4-year overall survival (OS) and event-free survival (EFS) are 72% and 68%, respectively. For patients proceeding to SCT, the 4-year OS and EFS are 79% and 73%, respectively. All patients who received allografts are alive without disease at 38-141 months since diagnosis. For patients who received autografts, the 4-year EFS is 69%. Bone marrow involvement was a significant prognostic factor predicting for a worse survival (P = 0.02). CONCLUSION: A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.

Suitable whole blood levels 2 hours after neoral in liver transplant patients: experiences at a single center.

UNLABELLED: Whole blood levels 2 hours after Neoral (C2) administration were observed to correlate better with area under the curve (AUC(0-4)) than trough levels (C0), suggesting that C2 may be the best single time point predictor of Neoral absorption. Owing to concerns about drug toxicity due to excessive immunosuppression, C2 adjustments to target blood levels may represent an advance. The present study measured C2 and levels to determine which correlated more closely with AUC(0-4). METHODS: Between August 2003 and July 2004, 40 adult liver transplantations were performed in our center. All patients received Neoral twice daily. They were maintained at a C0 level of about 200 ng/mL. C0 levels were measured daily. C2 levels were estimated on postoperative days 3, 5, 7, 14, and 28. AUC(0-4) performed on postoperative days 3, 7, and 28 was calculated using the trapezoidal rule. RESULTS: The mean AUC(0-4), C0, C1, C2, C3, and C4 were 1100.3 +/- 484.8 ng/mL, 197.1 +/- 84.7 ng/mL, 240.7 +/- 166.2 ng/mL, 307.8 +/- 162.6 ng/mL, 302.8 +/- 138.9 ng/mL, and 300.3 +/- 142.8 ng/mL, respectively. C2 correlated with AUC(0-4) (R2 = 0.868: P < .05) better than C0 (R2 = 0.245: P < .05), C1 (R2 = 0.604: P < .05), or C4 (R2 = 0.583: P < .05). CONCLUSIONS: Neoral dose monitoring according to a mean C2 range of 307.8 +/- 162.6 ng/mL correlated better with AUC(0-4). Further studies are required to determine suitable C2 levels in liver transplant patients.

Shifting to outpatient management of acute myeloid leukemia: a prospective experience.

BACKGROUND: We assessed the feasibility of outpatient chemotherapy and supportive care in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: All patients receiving curative intent chemotherapy between 09/01 and 10/02 and meeting our criteria received supportive care post induction chemotherapy as well as their entire consolidation chemotherapy cycles as outpatients. Patients received antimicrobial prophylaxis; those developing episodes of fever and not meeting the criteria for admission were treated with outpatient intravenous antibiotics. RESULTS: Seventy-one cycles of induction chemotherapy were administered for newly diagnosed or relapsed AML. In 25 cycles the patient was discharged post chemotherapy prior to count recovery. Of these, 14 patients developed one or more febrile episodes as an outpatient and nine (36%) required readmission to hospital. Sixty-seven consolidation cycles were given on an outpatient basis. In 39 cycles there was one or more febrile episodes and in 14 (21%) admission was required. Infections were documented in four cases during induction and in 27 during consolidation. There were no treatment-related deaths. CONCLUSIONS: Outpatient management of AML is safe and feasible using the strategies outlined in this report.

Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease.

In all, 30 patients with CLL proceeded to myeloablative allogeneic BMT using related (n=20, 67%) or unrelated (n=10) donors, at the Princess Margaret Hospital (Toronto) (n=20) or the Leukemia/BMT Program of BC (Vancouver) (n=10), from 1989 to 2001. Median (range) interval from diagnosis to BMT was 4.8 (0.3-13) years, median number of prior therapies was three and median age 48 years. The preparative regimen included total body irradiation in 15 (50%). In all, 14 of 30 patients (47%) are alive, with median (range) follow up of 4.3 (2.4-10.5) years. All are in complete remission, two following therapy for post-BMT progression. Actuarial overall (OS) and event-free survival (EFS) at 5 years is 39% (OS 48% for related donor and 20% for unrelated donor BMT); cumulative incidence of nonrelapse mortality (NRM) and relapse is 47 and 19%, respectively. Both acute (RR=0.008, P=0.01) and chronic (RR=0.006, P=0.02) Graft-versus-host disease (GVHD) were associated with markedly decreased risk of relapse. Patients receiving grafts from unrelated donors had increased NRM (RR=3.6, P=0.02) and decreased OS (RR of death=3.4, P=0.002). Allogeneic BMT has resulted in long-term EFS in approximately 40% of patients with CLL. There is evidence for a strong graft-versus-leukemia effect associated with acute and chronic GVHD, resulting in near complete protection from relapse.

Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia?

Although continued advances have been made in the treatment of acute myeloid leukemia (AML), approximately 20-30% of patients will never achieve a remission. For these patients with primary refractory AML, the only curative option remains an allogeneic stem cell transplant. Allogeneic transplantation provides the ability to administer myeloablative doses of chemotherapy or chemoradiotherapy, as well as the advantage of a possible graft-versus-leukemia effect. Difficulty in interpreting the literature is due to selection bias, in particular, the varying definitions of primary refractory disease with respect to the morphological criteria and the number of induction regimen required before being defined as being refractory. Regardless, it is a procedure with high treatment-related mortality and risk of relapse. Most studies demonstrate an event-free survival of 10-20% at 5 years. Predictive factors of outcome include blast cell count in the marrow, karyotype, the number of prior regimen, age, performance status and availability of a related donor. These prognostic factors should be considered prior to offering allogeneic transplantation for primary refractory AML. Those patients with many favorable prognostic factors and an HLA-matched related donor available would be the best candidate for the procedure. Those with many poor prognostic factors and only an unrelated donor available may be better served by being offered palliation or being enrolled in investigational studies.

Characteristics and outcome of patients developing endocarditis following hematopoietic stem cell transplantation.

Endocarditis is an uncommon complication of hematopoietic stem cell transplantation (HSCT). A retrospective review of 1547 patients who underwent HSCT in Vancouver between January 1986 and December 2001 was performed. In all, 20 cases of endocarditis were identified (1.3% of all patients) with nine patients having received cryopreserved autologous stem cells, six stem cells from a histocompatible sibling and five patients stem cells from an unrelated donor. Five patients had endocarditis diagnosed while alive, a median of 6 months post-HSCT, by transthoracic (four patients) or transesophageal (one patient) echocardiography. The remaining 15 cases of endocarditis were only identified post mortem. The mitral valve was the most frequently involved (10 patients) followed by the aortic valve (six patients); multivalvular disease was noted in five patients. Of the 11 affected allogeneic HSCT patients, 10 had previously developed acute graft-versus-host disease (GVHD). Causative organisms were identified in 11 patients, while nine additional cases were felt to be thrombotic in origin. Of the 20 patients, 19 died with the sole survivor alive 10 years following an aortic valve replacement. Endocarditis is an uncommon complication of HSCT usually involving the cardiac valves on the left side of the heart and is associated with a high mortality rate.

Subdural hematomas during CML therapy with imatinib mesylate.

Seven of one hundred twenty-one patients with chronic myeloid leukemia (CML) treated with imatinib mesylate developed subdural hematomas. All had advanced disease and were treated initially at a dose of 600 mg per day. Three patients had thrombocytopenia (platelet < 10 x 10(9)/l), one had leukocytosis (white blood cell count > 150 x 10(9)/l) and three had neither around the time of diagnosis of the subdural hematomas. Four patients required surgical evacuation. One patient, in blast crisis, died as a consequence of the subdural hematoma. Three patients survived but died of progressive CML. The remaining three patients having recommenced imatinib, are alive and well, and one has achieved a major cytogenetic response. Subdural hematomas must be considered even in mildly symptomatic patients receiving imatinib regardless of their peripheral blood counts. Patients who survive can be cautiously restarted on imatinib. Further studies are required to study the potential relationship between imatinib mesylate and subdural hematomas.

Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis.

To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P<0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P<0.001, 8.1 (2.2-20.7) P=0.002 and 1.98 (1.1-3.2) P=0.009, respectively. In multivariate analysis, age >or=35 years at the time of AHSCT (P=0.001) and an interval from diagnosis to AHSCT >or=36 months (P=0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.