Allogeneic stem cell transplant for myelofibrosis- A retrospective single-center study.

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment option for myelofibrosis (MF). Despite the benefits of long-term relapse-free survival, HSCT can be associated with substantial treatment-related morbidity and mortality. Methods: This is an observational retrospective study of 15 consecutive patients with MF who underwent allogeneic HSCT at a tertiary care center in Northern India between June 2012 and January 2020. The pre-transplant Dynamic International Prognostic Scoring System (DIPSS) and hematopoietic cell transplantation-specific co-morbidity index (HCT-CI) scores were used. The primary endpoints were overall survival (OS) and disease-free survival (DFS), and the secondary endpoints were post-transplant complications (acute and chronic graft-versus-host-disease [GvHD], graft failure [GF], and cytomegalovirus reactivation [CMV]). Results: The OS and DFS in our study were 60% with no relapse at a median follow-up of 364 days (range 7-2,815 days). Twenty-seven percent of patients developed acute GvHD and 27% of patients developed chronic (limited) GvHD. The non-relapse mortality (NRM) was 40%, with the main cause of death being sepsis, followed by acute GvHD. Conclusion: MF remains a challenging condition to treat, with a poor prognosis. Our study showed that reduced toxicity conditioning provided good DFS and OS. Thus, it should be offered to patients with high DIPSS scores. Sepsis was the predominant cause of mortality in this cohort.

Flow Cytometric DNA Ploidy Analysis in Haemato-Lymphoid Neoplasms: An Analysis of 132 Cases.

Background: FxCycleTM Violet (FCV) based flow cytometric (FCM) DNA ploidy analysis is a rapid and simple tool that can substantiate in characterizing the biological behaviour across the spectrum of haematological malignancies and correlates with cytogenetic studies. Materials and Methods: In this prospective study, we performed simultaneous immunophenotyping with FCV based on ploidy analysis in n=132 consecutive new samples, comprising n=110 samples of haemato-lymphoid neoplasms, including acute leukemias (n=67, 60.9%), CML with myeloid blast crisis (n=1, 0.9%), MDS with excess blasts (n=2, 1.8%), mature B cell/ T cell neoplasms (n=37, 33.7%), multiple myeloma (n=3, 2.7%) along with n=22 normal samples. The FCM DNA data was compared with corresponding conventional karyotyping results, wherever available. Results: In FCM ploidy analysis (n=110), the overall DNA index (DI) ranged from 0.81 to 2.17 and S-Phase fraction (SPF) from 0.1-31.6%. Diploidy was seen in n = 90 (81.8%), low-hyperdiploidy in n = 10 (9.1%), high-hyperdiploidy in n = 7 (6.4%) with one case each (0.9% each) having near-tetraploidy, high-hypodiploidy and low-hypodiploidy. The DI of all viable cell populations in normal samples ranged from 0.96-1.05. Conventional karyotyping was performed in n=76/110 cases (70%) with n= 11/76 (15%) culture failures. The modal chromosome number ranged from 45 to 63. A concordance of 95.4% (n=62/65) was noted with corresponding FCM DI. Conclusion: FCV-based ploidy is a sensitive technique that provides complementary information and ascertains a strong correlation with conventional cytogenetics across all haemato-lymphoid neoplasms. It can detect aneuploidy in all B-ALL and myeloma cases, even in hemodiluted samples with cytogenetic culture failure; supplement the diagnoses of erythroleukemia, and provide a useful screen for a higher grade lymph node disease in lymphoma cases with SPF > 3%.

Hematopoietic Stem Cell Transplant for Hematological Malignancies: Experience from a Tertiary Care Center in Northern India and Review of Indian Data.

Sanjeev Kumar SharmaHematopoietic stem cell transplantation (HSCT) is the preferred treatment for high-risk and relapsed/refractory hematological malignancies. Moreover, with the improved supportive care and increasing acceptance of haploidentical transplantations as an alternative treatment modality, more patients are opting for HSCT as a definite treatment for hematological malignancies. We report here the real-world data and outcome of HSCT done for hematological malignancies at our transplant center. Five hundred and sixteen patients underwent HSCT from August 2010 to November 2019. The most common indications for allogeneic and autologous HSCT were acute myeloid leukemia and multiple myeloma, respectively. The 5-year overall survival and disease-free survival for all transplants were 65% and 33%, respectively. Though outcome of matched sibling donor allogeneic transplant is better than haploidentical donor (HID) transplant, patients having only HID can still be considered for allogeneic HSCT for high-risk diseases. The most common cause of death was infections followed by relapse of the disease.

Outcomes of COVID-19 in Hematopoietic Stem Cell Transplant Recipients: Multicenter Retrospective Analysis.

COVID-19, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization on March 9, 2020. Hematopoietic stem-cell transplantation (HSCT) recipients may be highly susceptible to infection and related pulmonary complications due to nascent immune systems or organ damage from treatment-related toxicities. Poor outcomes in such group of patients were linked to older age, steroid therapy at the time of COVID-19 infection, and COVID-19 infection within a year of HSCT. We studied a cohort of 28 hematopoietic stem cell transplant recipients (male 17, M:F ratio of 1.5) with COVID-19 infection from 1st June 2020, through 31st December 2020 for outcome. Fever was the most common symptom at the time of presentation in 22 (78.5%) patients. Mortality rate at Day 28 and Day 42 was found to be 4/28 (14.3%) and 7/28 (25%) respectively. Patients within one year of HSCT and severe infection had higher day 28 mortality (with p values = 0.038)". There was no relation of mortality with type of transplant.

Myeloablative Versus Reduced Intensity Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplant for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Retrospective Analysis.

The conditioning regimens used for the allo-HSCT include either myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) regimens based on the age, performance status and co-morbidities. Studies comparing the survival outcomes of RIC and MAC allo-HSCT in AML and MDS patients have reported contradictory results. We therefore retrospectively analyzed our data of AML and MDS patients who received MAC and RIC allo-HSCT at our center and compared the long term outcome of the two conditioning regimens. One hundred twenty six consecutive patients were evaluated, 32 (25.4%) underwent MAC allo-HSCT and 94 (74.6%) underwent RIC allo-HSCT. The most common MAC regimen used was busulfan plus cyclophosphamide and the most common RIC regimen used was fludarabine plus melphalan. The median age was higher in RIC group (44 years, range 4-75 years) compared to MAC group (31 yrs, range 6-51 yrs, p = 0.001). There was no significant difference in terms of overall survival (p = 0.498), relapse-free survival (p = 0.791) and non-relapse mortality (p = 0.366) between the two groups. In multivariate analysis, only chronic graft-versus-host disease resulted in decreased risk of relapse and improved overall survival irrespective of the conditioning regimens used.

T-cell replete Haplo-identical HSCT with Post transplant Cyclophosphamide for Hemoglobinopathies: A retrospective analysis from a single center.

We report herein haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) by T-cell replete graft infusion, with post-transplant cyclophosphamide (PTCy) in patients with hemoglobinopathies. Patients received a conditioning regimen consisting of either busulfan, fludarabine, cyclophosphamide, with antithymocyte globulin or Thiotepa, antithymocyte globulin, fludarabine, cyclophosphamide, and TBI. The median follow-up period was 14.3 months (range, 1-63 months). Overall survival (OS) and disease-free survival (DFS) were 80% and 62.8%, respectively. Incidence of secondary graft failure was 14%. Incidences of acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) were 22.5% and 20%, respectively. Cytomegalovirus (CMV) reactivation was observed in 42.5% of cases. The 100-day mortality rate was 20%, with sepsis and aGvHD being the predominant causes of death.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

Hematopoietic Stem Cell Transplantation for Fanconi Anemia: A Single Center Experience from India.

Hematopoietic stem cell transplantation (HSCT) is the only treatment option for the hematological manifestations of Fanconi anemia (FA). Fludarabine based reduced intensity conditioning regimens have helped in improving outcomes significantly in FA patients. We retrospectively analyzed the outcomes of FA patients who underwent allogeneic HSCT at BLK Superspeciality Hospital, New Delhi from June 2011 to September 2019. Twenty FA patients underwent 23 transplants at our center. Overall survival and disease free survival were 65% and 50%, respectively at a median of 23 months. Overall mortality was 30%. HSCT for FA is a feasible option even in developing countries although children present late to transplant centers after multiple transfusions and infections.

Cytarabine ears - A side effect of cytarabine therapy.

Cytarabine, a pyramidine analog, is used for treating various hematological malignancies such as acute leukemias and lymphomas. Side effects of cytarabine are dose dependent and include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, hepato-renal insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity and dermatological side effects. The dermatological side effects can be immediate or due to delayed hypersensitivity reactions. They have been attributed largely to release of cytokines. We present three such cases of delayed hypersensitivity to cytarabine affecting the ears bilaterally.

Tacrolimus Induced Diabetic Ketoacidosis Following Hematopoietic Stem Cell Transplantation.

Risk of diabetes mellitus increases after solid organ and hematopoietic stem cell transplantation. Diabetic ketoacidosis has been reported after solid organ transplantation in patients receiving tacrolimus but has rarely been reported after stem cell transplantation. The major risk factors for diabetic ketoacidosis are immunosuppressive drugs used after transplantation. We report here three cases of allogenic stem cell transplant who developed diabetic ketoacidosis while on treatment with tacrolimus. The drug was stopped in all the cases and patients were treated with insulin therapy resulting in complete recovery from diabetic ketoacidosis.

Summary of the Highlights of 2019 ASTCT Meeting by iNDUS BMT Group at Chennai, India.

This article summarises the main highlights of the abstracts presented at the annual meeting of American Society of Transplantation and Cellular Therapy (ASTCT). The highlights of ASTCT meeting were organised by iNDUS BMT group in Chennai, India. The purpose of the highlight meeting was to educate the students about the latest research in the field of hematopoietic stem cell transplantation and its applicability for the developing country perspective.

Severe hypersensitivity allergic reaction to filgrastim in a healthy stem cell donor.

INTRODUCTION: Granulocyte-colony stimulating factor (G-CSF) has been approved for use for mobilization of hematopoietic progenitor cells from the marrow into the blood for peripheral blood stem cell collection. Commonly reported side effects of G-CSF include deep throbbing bone pain, severe myalgia and leucocytosis. CASE REPORT: We describe a case of severe hypersensitivity anaphylactoid reaction after filgrastim administration in a healthy stem cell donor. This haploidentical donor was a 38-year old man with sickle cell trait, donating stem cells for his son, a case of sickle cell disease. On administration of G-CSF (10 µg/kg) he developed features of anaphylaxis. MANAGEMENT AND OUTCOME: He was given supportive care with oxygen, IV fluid bolus, anti histaminics and steroids. The donor had complete recovery and underwent successful bone marrow harvest. CONCLUSION: There have been various reports of hypersensitivity anaphylactoid reactions in patients undergoing chemotherapy but those associated with the first dose of G-CSF in healthy stem cell donors have rarely been reported.

Allogenic Hematopoietic Cell Transplantation in Thalassemia Major: A Single-center Retrospective Analysis From India.

Thalassemia is a major public health problem in developing countries. Sibling matched hematopoietic stem cell transplantation (HCT) is the recommended treatment for thalassemia major (TM). We retrospectively analyzed our data of thalassemia major patients who underwent HCT at a tertiary care center in Northern India from January 2008 to September 2017. The primary end points were overall survival (OS) and thalassemia-free survival (TFS), and secondary end points were complications post HCT (graft-versus-host-disease [GVHD], hemorrhagic cystitis [HC], and sinusoidal obstruction syndrome [SOS]). Data of 203 transplants for 200 patients (3 s transplants) were evaluated. Median follow-up period was 29.1 months (range, 0.3 to 116.7 mo). The overall survival (OS) was 88.5% and TFS was 82%. Class risk analysis showed a significantly higher OS and TFS in class I and class II compared to class III high risk group (OS: P=0.0017; TFS: P=0.0005) and (OS: P=0.0134; TFS: P=0.0027) respectively. Acute and chronic GVHD was seen in 59 (29.5%) and 18 (9%) patients, respectively, and SOS and HC were seen in 23 (11.5%) and 11 (5.5%) patients, respectively. This study reconfirms that allogenic HCT is feasible in developing world with the overall survival and TFS comparable to that reported in Western literature and should be considered early in all TM patients with available matched sibling donors.

Gastrointestinal Biopsies for Evaluation of Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Patients.

Graft-versus-host disease (GVHD) is the major complication post hematopoeitic stem cell transplantation (HSCT) causing significant morbidity and mortality. Colonic biopsies were performed in 25 post HSCT patients presenting the diarrhea for diagnosis of acute graft versus host disease (A-GVHD). The present study was undertaken to evaluate and illustrate histomorphological features of A-GVHD in GI biopsies and to grade them. Histopathological features of gastrointestinal biopsies from 25 allogeneic HSCT patients having clinical suspicion of A-GVHD were evaluated and compared with colonic biopsies from negative controls. A-GVHD was observed in 17 cases, CMV colitis was present in 3 cases and one case had herpes simplex infection diagnosed in conjunction with serological findings. A-GVHD was graded as grade 1 and 2 in 10 cases and grade 3 and 4 in 7 cases. Apoptosis of crypt epithelial cells was the cardinal feature for diagnosis. Grade 1 and grade 2 A-GVHD cases showed crypt apoptosis in all cases as well as pericryptal apoptosis in lamina propria in many cases. Occasional crypt loss was seen in grade 2 GVHD. Inflammatory infiltrate was composed of lymphocytes and plasma cells. Neutrophils were inconspicuous. Grade 3 and grade 4 A-GVHD cases showed contiguous areas of multiple crypt loss and ulceration with inflammatory infiltrate predominantly composed of lymphocytes and plasma cells, but neutrophils were more prominent than in grade 1 and 2 A-GVHD. Apoptosis of crypt epithelial cells was present in all grade 3 &4 cases except one case. CMV cases were diagnosed by CMV inclusions and IHC stain. Several factors including drug-induced side effects and infections can cause difficulty in histologic interpretation of gastrointestinal biopsies for GVHD. Proper histomorphological interpretation of intestinal A-GVHD is critical for clinical management. A-GVHD is treated with immunosuppression which may worsen infective condition, if present.

Outcome of 51 autologous peripheral blood stem cell transplants after uncontrolled-rate freezing ("dump freezing") using -80°C mechanical freezer.

BACKGROUND AND OBJECTIVE: Controlled-rate freezing is a complicated, expensive, and time-consuming procedure. Therefore, there is a growing interest in uncontrolled-rate freezing (UCF) with -80°C mechanical freezers for cryopreservation of hematopoietic stem cells. This is a retrospective analysis of efficiency of UCF and outcome of autologous peripheral hematopoietic stem cell (PBSC) transplants at our center from December 2011 to June 2016. MATERIALS AND METHODS: Cryoprotectant solutions used included 5% dimethyl sulfoxide and 5% albumin with 2% hydroxyethyl starch and stored at -80°C mechanical freezer till transplant. Evaluation of cryopreservation was studied by analyzing the variation in cellularity, viability, and CD34+ stem cell dose recovery as well as clinical follow-up with engraftment. RESULTS: A total of 51 patients (23 females and 28 males) underwent autologous PBSC transplantations with a median age of 31 years (range: 3-60 years) for both hematological and nonhematological indications. Mean recovery post by UCF at -80°C mechanical was 92.9% ± 15.5% for nucleated cells, 86.6% ± 15.5% for viability, and 80% ± 21.5% in CD34+ dose. The median day to neutrophil engraftment was 10 (range 5-14 days) and platelets engraftment was 15 (range 8-45 days). The cryopreserved products were stored at -80°C for median 7 days (range 2-41 day) before transplant. DISCUSSION/CONCLUSION: Our analysis shows that PBSC can be successfully cryopreserved with mechanical uncontrolled rate freezing. This is a cheap and simple method to freeze the stem cells for a short period in resource-constrained setting.