A Deeper Depth of Response After Salvage Therapy Improves Outcomes of Autologous Stem Cell Transplantation in Relapsed Lymphoma and the Feasibility of Non-controlled Rate Freezing of Peripheral Blood Stem Cells.

Background High-dose chemotherapy followed by autologous stem cell transplantation is considered a standard treatment approach for patients with relapsed Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL). The goal of autologous stem cell transplant in relapsed lymphoma is to achieve long-term disease control, i.e., cure, in contrast to disorders like multiple myeloma, where it only prolongs the duration of remission, progression-free survival, and improves the quality of life. Published outcomes of high-dose therapy and ASCT and the impact of different factors affecting survival in low- to middle-income countries are very limited. Our study analyzed all the autologous stem cell transplants performed in our center over a six-year period to ascertain engraftment, responses, outcomes, and variables that may have impacted transplant outcomes. Methods We conducted a retrospective study including 76 patients from January 2015 to December 2020. Data were retrieved from electronic medical records at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results Out of a total of 82 autologous transplant patients, 76 were eligible for the study, out of which 50 (66%) had HL and 26 (34%) had NHL. The median age was 29 years (range 18-53) and 29 years (range 20-45) for HL and NHL, respectively. The male-to-female ratio was 5:2 and 4:1 for HL and NHL, respectively. The majority had advanced-stage disease, 85% in HL and 75% in NHL. The minimum cell dose infused was 2.5 million CD34+ cells/kg. Median days to platelets and ANC engraftment were 14 and 11 days, respectively. The 30-day transplant-related mortality was 8.9% and 7.4% in HL and NHL, respectively. The 100-day mortality was 15.2% and 11% in HL and NHL, respectively. The two-year disease-free survival (DFS) and overall survival (OS) were 83% and 83%, respectively, in HL patients. The two-year DFS and OS were 78% and 85%, respectively, in NHL patients. Conclusion High-dose therapy and autologous stem cell transplantation in low- to middle-income countries are limited to relatively younger patients, potentially curative conditions such as lymphoma, and predominantly after achieving a complete response to salvage therapy due to limited resources. Due to these factors, our study shows excellent response rates and survival outcomes compared to internationally published data. Engraftment was also excellent and comparable to published data despite the non-controlled rate freezing of peripheral blood stem cells.

Management of Acute Lymphoblastic Leukemia During Pregnancy: A Case Report and Review of the Literature.

Acute lymphoblastic leukemia (ALL) during pregnancy necessitates treatment with high-dose chemotherapy, which can threaten the lives of both the mother and fetus. The aim of the treatment not only focuses on selecting and administering optimal chemotherapy with appropriate doses to the mother but also reflects the crucial understanding of the fetal gestational age at the time of administration of chemotherapy to minimize fetal exposure. We describe the case of a 19-year-old patient diagnosed with ALL at 29 weeks gestation. She received treatment in the third trimester with the Berlin-Frankfurt-Munster (BFM) 2000 induction chemotherapy protocol consisting of a combination of daunorubicin, vincristine, pegaspargase, prednisolone, and intrathecal (IT) methotrexate and gave birth to a healthy baby girl via vaginal delivery four weeks after initiating the induction of chemotherapy.

Significance of CMV reactivation in non-allogeneic stem cell transplant patients with cancers: experience of single tertiary care cancer institute.

CMV reactivation is rare in hematological as well as solid organ malignancies in non-allogeneic stem cell transplant settings. An increasing number of patients undergoing active treatment or follow-up and diagnosed with CMV reactivation in recent years prompted us to investigate the risk factors and outcomes of CMV reactivation or disease. This was a hospital-based retrospective study that included 174 cancer patients suspected of CMV reactivation. Among them, forty-one tested positive for CMV viremia. The risk factors for CMV reactivation included the use of steroids in 78% of patients, active cancer in 43.9%, use of a monoclonal antibody rituximab in 31.7%, a history of radiation in 26.8%, and autologous stem cell transplant in 12% of patients. The median age was 36 years, and the most common clinical feature was fever (58.5%; n = 24), followed by GI symptoms (12.1%; n = 5), respiratory symptoms (14.6%; n = 6), cytopenia (7.3%; n = 3), and visual/neurological symptoms (4.8%; n = 2). The mean CMV viral load was 37,332 copies/ml (range: 75.00-633,000.00 copies/ml). Nineteen patients received CMV treatment with an average treatment duration of 81.5 days. The median overall survival was 2 months, with 12.0% of patients alive at 5 years. CMV reactivation is associated with significant morbidity and mortality. We recommend vigilant monitoring of CMV-related symptoms, with a low threshold for testing and treatment, for patients with multiple risk factors for CMV reactivation.

Developing an Allogeneic Hematopoietic Progenitor Cell Transplant Service in a Resource-Limited Country: Challenges and Outcomes.

Introduction Allogeneic stem cell transplant has curative potential for many hematological disorders. Building an allogeneic hematopoietic progenitor cell transplant (HPCT) unit requires huge investment, infrastructure, equipment, medical supplies, and training of health care professionals. The key objective of this study is to share our experience of developing an allogeneic HPCT service at our tertiary care cancer hospital in a low-middle-income country. In addition, this study presents the outcomes of the first 30 allogeneic HPCTs done at our center. Methods This retrospective observational study included adult patients 18 years old or older with hematological malignancies who underwent allogeneic HPCT between July 2019 and April 2023 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Result Of the 30 patients, 24 underwent matched sibling donor (MSD) transplants in which a myeloablative-conditioning regimen (MAC) was used in 19, and a reduced conditioning regimen (RIC) was used in one. Of the six haploidentical-related donor transplants, four received MAC, and two received RIC. The median recipient age at HPCT was 23 and 21 years for MSD and Haplo-related donor transplants, respectively. The median follow-up duration was 12 months (Range: 10 days - 33 months). The overall survival rate at one year was 71.3% among all allogeneic stem cell transplant patients, whereas the disease-free survival rate at one year was 63.7%. In the acute lymphoblastic leukemia group, the disease-free survival rate at one year post allograft was 51.5%, while in the acute myeloid leukemia group, it was 78.7%. Conclusion This study demonstrates the successful development of an allogeneic bone marrow transplant unit at our hospital despite significant financial constraints. This has allowed us to provide a potentially curative and life-saving treatment to a substantial number of cancer patients. The bone marrow transplant outcomes of this study are comparable to those reported by international bone marrow transplant registries.

Haematopoietic Stem Cell Transplant Trends in Pakistan: Activity Survey from Pakistan Bone Marrow Transplant Group.

Pakistan is the fifth most populous country with a population of 225 million and has health expenditure accounting for only 2.8 percent of gross domestic product (GDP). Accordingly, there are a limited number of haematology-oncology and transplant centers in the country. The Pakistan Blood and Marrow Transplant (PBMT) group was established in 2020, and this report is the first activity survey from January 2021 to December 2022 focusing on the trends of matched-related donor, haploidentical, and autologous transplants in a developing country. A total of 12 transplant centers contributed data on the modified PBMT survey form retrospectively and 806 haematopoietic stem cell transplants (HSCTs) were carried out during the study duration. Allogeneic HSCT constituted 595 (73.8%) of all the transplants; this is in stark contrast to Western data, where autologous HSCT accounts for the majority of transplants. ß-thalassemia major and aplastic anemia were the commonest indications for allogeneic HSCT, in contrast to Western data, where acute leukemia is the leading transplant indication. Autologous transplants were more frequently performed for Hodgkin's lymphoma as compared to non-Hodgkin's lymphoma and multiple myeloma. The use of peripheral and bone marrow stem cells was comparable. A myeloablative conditioning regimen was routinely used in patients with acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.

Bleomycin-Induced Fulminant Hyperpyrexia: A Report of Two Cases and Review of Literature.

Bleomycin is a commonly used cytotoxic agent that has proven its efficacy over the years. Though a common part of many protocols targeting lymphomas and germ cell tumors, it does have some serious adverse effects. Bleomycin is notorious for pulmonary toxicity and very rarely may cause fulminant hyperpyrexia. We describe two cases of classical Hodgkin's lymphoma (cHL) developing acute fulminant hyperpyrexia after administration of the first dose of bleomycin as part of chemotherapy protocol. This is a rare adverse reaction that closely mimics anaphylaxis and has an unpredictable and possibly fatal course. Health care professionals involved in the administration of chemotherapy need to be very vigilant in monitoring for symptoms of this reaction.

Cytomegalovirus Reactivation in Patients With Acute Lymphoblastic Leukemia in Non-transplant Setting.

Acute lymphoblastic leukemia is predominately a childhood disease and around two third of cases are of B-cell phenotype. Cytomegalovirus is an important cause of morbidity and mortality in allogeneic hematopoietic progenitor cell transplant; however, it is rare in patients with B-cell acute lymphoblastic leukemia in non-transplant settings. In this study, we evaluated 72 patients of acute precursor (pre) B-cell acute lymphoblastic leukemia at Shaukat Khanum Memorial Cancer Hospital and Research Center, out of which three were positive for Cytomegalovirus.

Outcomes of Philadelphia Positive Acute Lymphoblastic Leukemia in Adolescent and Young Adults.

Background Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) accounts for 25% of acute lymphoblastic leukemia cases in the adolescent and young adult (AYA) age subgroup. It is associated with poor outcomes and is considered a standard indication for allogeneic stem cell transplant (Allo-SCT). Improved outcomes have been reported with addition of tyrosine kinase inhibitors (TKIs) to chemotherapy in children and the role of Allo-SCT is now being debated in the first remission. Complete response (CR) at three months is associated with improved survival even without Allo-SCT in first CR. In this study, we have analyzed disease-free survival (DFS), overall survival (OS), and factors affecting survival outcomes of Ph+ ALL in the AYA subgroup, in resource-limited settings treated with chemotherapy and TKIs. Materials and methods This is a retrospective, multicenter cohort study of Ph+ ALL AYA patients, aged 18-40 years, and registered between January 2015 and December 2020. Primary objectives are to calculate disease-free survival (DFS) and overall survival (OS). Secondary objectives are to identify prognostic factors affecting response rates and outcomes. List of cases was obtained from hospital information system (HIS) and data were collected from patient case notes and electronic medical records. Data analysis was done utilizing the SPSS statistical program (Armonk, NY: IBM Corp.). Results Forty-nine patients were identified with Ph+ ALL with a median age of 23 years (range: 18-40 years) and a male-to-female ratio of 2.5:1. None of the patients had central nervous system (CNS) disease. White cell count was >30,000 per mm3 in 26% of patients, while 13% had additional cytogenetic abnormalities. Thirty-three percent patients received adult (hyper-cyclophosphamide, vincristine, Adriamycin, and dexamethasone {CVAD}) protocols while 67% received pediatric-inspired (Berlin-Frankfurt-Munster {BFM} 2000 or UK-ALL 2003/2011) protocols. TKI therapy was received by 66% of patients during treatment (early: 37%; late: 29%) and 34% did not receive TKIs due to financial constraints. CR after induction was achieved in 69% cases. Induction mortality was 16%. The median DFS for the entire cohort was 27 months (0.93-53.06) and the median OS was 29 months (8.89-49.10). The median OS in Allo-SCT group was not reached vs 8.0±8.8 months (p=0.05) with chemotherapy only. The OS was significantly better in patients with no additional cytogenetic abnormalities, pediatric-inspired chemotherapy protocols, early use of TKIs in induction phase, Allo-SCT, and post-Allo-SCT use of TKIs. Conclusion Addition of TKIs to pediatric-inspired chemotherapy protocols in Ph+ ALL AYA patients and Allo-SCT results in better overall survival. TKI availability remains a significant issue in low-income countries due to significant financial burden on the patients. Allo-SCT continues to be an attractive option, particularly in low-income countries providing an option for cure in Ph+ ALL.