Haematopoietic Stem Cell Transplantation

Abstract One hundred and fifty four patients received allogeneic stem cell transplant from HLA matched siblings for various haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to Sep 2006. Indications for transplant included aplastic anaemia (n=66), b-thalassaemia major (n=40), CML (n=33), acute leukaemia (n=8) and misc disorders (n=7). One hundred and twenty patients were male and thirty four were female. Median age of patient cohort was 14 yrs (range 1 ¼ −54 yrs). Pre-transplant infection surveillance was carried out and strict prophylaxis against infection was observed. The mean mononuclear cell dose was 4.2 x 109/kg of recipient. Post transplant complications encountered in our patients were: acute GvHD (grade II-IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jirovici infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. Certain unexpected rare post transplant complications were also observed in our patients. These included hickman catheter embolization, GB syndrome, deep vein thrombosis, haemorrhagic pericarditis with clots leading to cardiac temponade, idiopathic polycythemia, dengue fever and status epilepticus. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, relapse, intracranial haemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis and CMV infection. At five years, the overall survival (OS) and disease free survival (DFS) was 72.5% & 70.7% respectively.

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Post Allogeneic Stem Cell Transplant Complications - Single Centre Experience from Pakistan.

Blood ◽

10.1182/blood.v110.11.4955.4955 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4955-4955 ◽

Cited By ~ 1

Author(s):

Shahid Raza ◽

Khalil Ullah ◽

Parvez Ahmed ◽

Tariq Satti ◽

Badshah Khan

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Bacterial Infections ◽

Fungal Infections ◽

Chronic Gvhd ◽

Cell Transplant ◽

Acute Leukemias ◽

Post Transplant ◽

Infective Complications ◽

Transplant Complications

Abstract Over last five years 154 patients received HLA matched sibiling transplants at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. Indications for transplant included Aplastic anemia, B-Thalassaemia major, Chronic Myeloid leukemia, Acute leukemias, and miscellaneous disorders which included Myelodysplastic syndrome, Fanconi’s anemia, Non-Hodgkin lymphoma, and Gaucher’s disease. All patients received standard conditioning regimens and GvHD prophylaxis. Pre-transplant infection surveillance was carried out in all patients and strict prophylaxis against infection was observed as per our transplant policy. During post transplant follow up we encountered certain infective and non infective complications. These included: acute GvHD (grade II–IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jiroveci infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. We encountered certain rare unexpected post transplant complications which have been rarely reported in literature before. These included Hickman catheter embolization, Guillain Barre syndrome, co-infection with pneumocystis jirovicii and a rare fungus trichosporon beigilii, cyclosporine induced uncontrolled seizures, idiopathic polycythemia, haemorrhagic pericardial effusion with cardiac temponade, deep vein thrombosis, dengue fever and measles. These complications were effectively managed in our centre. There was only one death associated with these complications. Mortality was observed in 27.2% patients. Mortality related to non-infective complications was 14.2%. Major non-infective causes of mortality were GvHD, VOD, disease relapse, intracranial haemorrhage and acute renal failure. Mortality related to infections was 13%. Fatal infections included CMV disease, disseminated aspergillosis, pseudomonas septicaemia and tuberculosis.

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10.1093/med/9780199683307.003.0009 ◽

2015 ◽

Author(s):

Drew Provan ◽

Trevor Baglin ◽

Inderjeet Dokal ◽

Johannes de Vos ◽

Hassan Al-Sader

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Fungal Infections ◽

Chronic Gvhd ◽

Haematopoietic Stem Cell ◽

Sinusoidal Obstruction Syndrome ◽

Cell Transplant ◽

Post Transplant

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up

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Treatment dilemma for survivors of rituximab-induced bowel perforation in the setting of post-transplant lymphoproliferative disorder

BMJ Case Reports ◽

10.1136/bcr-2018-226666 ◽

2018 ◽

Vol 11 (1) ◽

pp. e226666 ◽

Cited By ~ 1

Author(s):

Brianne J Sullivan ◽

Grace J Kim ◽

Gabriel Sara

Keyword(s):

Monoclonal Antibody ◽

Stem Cell ◽

Lymphoproliferative Disorder ◽

Stem Cell Transplant ◽

Bowel Perforation ◽

Standard Of Care ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Tumour Lysis ◽

Post Transplant

Post-transplant lymphoproliferative disorder (PTLD) is a recognised complication of solid and haematopoietic stem cell transplant. It consists of a heterogeneous group of lymphoid neoplasms that arises secondary to post-transplant immunosuppression. Although there is no definite standard of care for the optimal treatment for PTLD, rituximab, a monoclonal antibody, with and/or without chemotherapy (usually CHOP=cytoxan, doxorubicin, vincristine, prednisone) has become a routine part of the treatment of any CD20 (+) PTLD, with response rates similar to chemotherapy with decreased toxicity. A rare and often lethal, complication of rituximab therapy for PTLD is bowel perforation secondary to tumour lysis of lymphoma involving the intestine. A small number of cases of bowel perforation have been reported, with very few documented survivors. The risk for recurrent perforation in the setting of ongoing rituximab treatment is unknown. There is sparse data supporting how to best treat the survivors.

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Valganciclovir Is Safe and Effective as Pre-Emptive Treatment for CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.5300.5300 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5300-5300

Author(s):

Rocco Pastano ◽

Federica Gigli ◽

Giovanna Andreola ◽

Liliana Calabrese ◽

Fedro Peccatori ◽

...

Keyword(s):

Stem Cell ◽

Oral Administration ◽

Intravenous Administration ◽

Oral Treatment ◽

Drug Formulation ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Cmv Infection ◽

Intravenous Ganciclovir ◽

Hematopoietic Stem

Abstract RATIONALE OF STUDY: Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection still represents an important cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplant (HSCT). The standard pre-emptive treatment is based on intravenous administration of Ganciclovir (GCV). Valganciclovir (VGC), the pro-drug formulation of GCV is characterised by an excellent bio availability, making this drug suitable for oral administration. PATIENTS: Since March 2003 all patients treated with reduced (27 patients) or fully ablative (3 patients) conditioning regimens followed by sibling HSCT, were monitored with bi-weekly CMV/PCR and pp65/assays. Overall 15 episodes of CMV positivity were detected in seven patients. Patients resulted positive (3 cells pp65+ or 1000/100000 PCR +) started oral treatment with VGC 900 mg bid, for the first fourteen days, followed by 900 mg q.d. up to at least seven days after assays normalization. The median duration of therapy was 21 days (range 10–21 days). No significant toxicity was observed. All patients had a normalization of CMV/PCR and pp65/assays within fourteen days, with a response rate (RR) of 100%. In two patients the oral VGC therapy was changed to the intravenous administration of Foscavir, because of concomitant neutropenia and acute GvHD. CONCLUSION: Pre-emptive treatment of CMV infection with VGC is safe, feasible and effective. Furthermore, the oral administration of this drug in an outpatient setting, reduces significantly the costs compared with a therapy that needs hospitalization as intravenous Ganciclovir.

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BK Virus (BKV) Associated Haemorrhagic Cystitis Is Associated with Graft Versus Host Disease (GVHD) and Significant Morbidity Post Haematopoietic Stem Cell Transplant (HSCT).

Blood ◽

10.1182/blood.v120.21.3040.3040 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3040-3040

Author(s):

Alesia Abigael Hunt ◽

Anjum Bashir Khan ◽

Donal McLornan ◽

Majid A Kazmi ◽

Matthew Streetly ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Chronic Gvhd ◽

Bk Virus ◽

Haematopoietic Stem Cell ◽

Control Group ◽

Cell Transplant ◽

Haemorrhagic Cystitis ◽

Graft Versus Host ◽

Grade Ii

Abstract Abstract 3040 The Polyomavirus hominis 1 BK virus (BKV) is a non-encapsulated DNA virus, which infects up to 90% of the world's population, and may reactivate at times of severe immunosuppression, including post haematopoietic stem cell transplantation (HSCT). The significance of BK virus reactivation post Haematopoietic Stem Cell Transplant (HSCT) remains unclear. We collected retrospective data on viruria, viraemia, haemorrhagic cystitis (HC) and acute/chronic graft versus host disease (a/cGVHD) in patients at our institution over the period 2006 to 2011. We compared with a multivariate matched control group of 38, who did not reactivate BK. The groups were matched for age, sex, donor source and conditioning regimen including use of Alemtuzumab. Global BK reactivation incidence was 32% (38/118) of allogeneic HSCT during this period. 73% (28/38) of those who reactivated received volunteer unrelated donor (VUD) grafts, and 50% (18/38) received Alemtuzumab. Patients were sub-divided into those with high grade viraemia (HGV, VL >104 copies/ml), 47% (18/38) or low grade viraemia (LGV, VL<104 copies/ml), 53% (20/38). HGV was present in 57% of VUD transplants and 20% of sibling recipients, compared to LGV in 29% of VUDs and 70% of siblings. HGV influenced 1 year EFS; 18% versus 55% in LGV. Median OS was 173 days in HGV versus 345 days in LGV. Cumulative mortality rate in the BK group was 71% (27/38) as compared to 55% (21/38) in the control group (not significant). Relapse related mortality in the BK group was 22% (6/27) versus 57% (12/21) in the control group, at a median follow up of 229 days (p=0.088), indicating the high incidence of non-relapse causes of mortality in the BK group. 79% (30/38) of patients reactivating BK developed aGVHD, including 83% (15/18) with HGV, compared to 57% (21/37) in the control group (p=0.039). The number of patients who developed grade II-IV aGVHD in the BK group was 30/38 (79%) and 11/37 (20%) in the control group (p <0.001), figure 1. In 33% of patients BK reactivation preceded aGVHD by a mean of 12 days. 84% (27/32) of patients developed cGVHD, compared to 30% (18/30) in control group (p=0.05). Moderate-severe (NIH grade) cGVHD was more prevalent in patients reactivating BK, compared to control group; 75% (24/32) versus 3% (1/30) (p<0.001), figure 2. This data suggests the association of BK with an increased incidence of acute and chronic GVHD, and significant morbidity. Notably 10 patients developed severe complications including grade 4 HC (5/10), obstructive hydronephrosis and bladder wall dysfunction requiring invasive intervention. 7/10 (70%) of these patients had HGV; 2 patients reactivated early, failed treatment, developed obstructive renal failure and died. These patients had an increased rate of mortality compared to the whole study group (p=0.005), and all failed to achieve an EFS of over 1 year. Of note, 8.5% of all allografts developed grade 4 HC and 90% of these subsequently died. BK reactivation strongly correlates with acute and chronic GVHD and an increase in non relapse mortality. Routine surveillance for BK with risk scoring may allow earlier detection and reduced morbidity of BK and GVHD. Further prospective studies are required to understand the impact of the reactivation of the virus. Figure 1: Cumulative Incidence of acute GVHD Grade II-IV: Figure 1:. Cumulative Incidence of acute GVHD Grade II-IV: p <0.001 Figure 2: Cumulative Incidence of chronic GVHD moderate-severe: Figure 2:. Cumulative Incidence of chronic GVHD moderate-severe: p <0.001 Disclosures: No relevant conflicts of interest to declare.

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A Novel Chemotherapy-Based Allogeneic Hematopoietic Stem Cell Transplant Regimen for Very Young Children with Leukemia.

Blood ◽

10.1182/blood.v120.21.3149.3149 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3149-3149

Author(s):

Susan E. Prockop ◽

Nancy A. Kernan ◽

Elizabeth G Klein ◽

Rachel Kobos ◽

Andromachi Scaradavou ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Young Children ◽

Cord Blood ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Free Survival ◽

Post Transplant

Abstract Abstract 3149 Young children in need of allogeneic hematopoietic stem cell transplant (HSCT) are at increased risk of unacceptable side effects from total body irradiation (TBI) and have historically been considered candidates for non-TBI containing regimens. However, disease free survival (DFS) has been poorer in cohorts of very young patients transplanted without TBI and novel chemotherapy based regimens are needed. We report results in a cohort of 14 children all under three years of age at the time of transplant (6 – 32 months; median 19.8 months) using a clofarabine-based ablative regimen. Fourteen patients in this age group have undergone transplant with a regimen consisting of clofarabine 20 mg/m2/day × 5, thiotepa 10 mg/Kg/day × 1 and melphalan 70 mg/m2/day × 2. All patients had high risk disease. Seven (7) pts were transplanted for ALL, 6 for AML and 1 for JMML. Patients with ALL or AML in first remission (CR1) or CR2, were categorized as patients with good risk disease while all other pts were considered as poor risk irrespective of all other factors. Transplant risk was good for 6/7 with ALL, and 3/6 with AML. The patient with JMML had stable disease. Stem cell grafts consisted of unmodified bone marrow (BMT) (N=6), double cord blood (dCBT) (N=7) and T cell depleted PBSCT (N=1). Donors were matched unrelated (N=5) or mismatched unrelated (N=9) including 7 double umbilical cord blood grafts, and one T cell depleted graft. Graft versus host disease (GvHD) prophylaxis was with tacrolimus and methotrexate for unmodified BMT, tacrolimus and mycophenolate for dCBT or T cell depleted HSCT. Two patients died early post transplant of infection (1) and acute GvHD (1). Neutrophil engraftment for the 13 evaluable patients was at a median of 13 days (10 –29 days) for PBSC and BM grafts and 17.5 days (12 –23 days) for recipients of CB grafts. Platelet engraftment for the 12 evaluable patients was at a median of 23 days (16 – 36 days) for recipients of PBSC and BM grafts and 43.5 days (36 –66 days) for recipients of CB grafts. In all five patients developed grade II-IV GvHD, and two patients chronic GvHD. Seven patients developed transaminitis which resolved in all cases. No patients developed Grade IV mucositis. One patient (AML) died after relapsing 5.5 months post transplant. Two patients are alive after relapsing at 1.3 months (AML) and 10.8 months (JMML) post-transplant. Nine of the 14 patients are alive in continuous complete remission seven of whom are greater than 36 months from transplant (40.2 – 71 months). The seven patients without chronic GvHD have had robust immune reconstitution, have responded to vaccination, and continue to meet growth and developmental milestones. Only one patient (transplanted at 14 months of age) has mild neurocognitive deficits. This novel chemotherapy based regimen is associated with durable engraftment of unmodified and cord blood HSCT grafts and promising disease free survival in very young children with leukemia. Based on the low toxicity profile in this cohort of patients higher dosing of clofarabine will be explored as a possible way to improve leukemia remission in the highest risk patients. Disclosures: Off Label Use: Clofarabine.

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Secondary neutropenia (SN) after autologous hematopoietic stem cell transplantation (AHSCT) in patients (pts) with lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6552 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6552-6552

Author(s):

Sunita Nathan ◽

John Joseph Maciejewski ◽

Elizabeth Shima Rich ◽

Parameswaran Venugopal ◽

Kent W. Christopherson ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Conditioning Regimen ◽

Stage Iv ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Post Transplant ◽

Cd34 Cells ◽

Transplant Complications

6552 Background: Plerixafor for mobilization of autologous stem cells (ASC) has increased the yield of transplanted ASC and is evolving as an important option for mobilization. A prior study reported a 10% incidence of SN after AHSCT (BMT 2009 Aug; 44(3): 175-83). Incidence and outcome of SN in the setting of Plerixafor/G-CSF (P/G), is unknown. We report the incidence and possible etiology for the development of SN in pts undergoing AHSCT for lymphoma at our institution. Methods: Data from 80 consecutive AHSCT pts over a 2 year period were reviewed. All pts were mobilized using P/G. Demographics, AHSCT indication, prior therapies (Rx), conditioning regimen (CR), engraftment and post-transplant complications were identified and collected. SN was defined as ANC <1000 after initial engraftment. Results: 80 pts underwent an AHSCT for lymphoma from 2009-11. 70 pts had evaluable data. 37 (52.86%) pts (average age 55.4 yrs) were male and 33 (47.14%) pts (average age 48.3 yrs) female. 25 (35.7%) pts had ≥2 comorbidities. Indications included relapsed/ refractory B-NHL, T-NHL and HL. 47 (67%) pts had Stage IV ds, 48.9% with BM involvement. 17 (24.3%) pts had >2 Rx, 18 (25.7%) with loco-regional XRT and 3 (4.3%) with RIT. CR included BEAM, BEC and Benda-EAM +/- Rituxan. # of CD34+ cells given ranged; 1.77-19.99 x 10^6/kg. Neutrophil engraftment occurred at a median of 11 days. 26 (37.14%) pts developed SN possibly from PCP prophylactic antibiotics and infections. Prior BM involvement, Rx or XRT had no role. 5 (45.4%) pts with Benda-EAM CR had SN. Associated morbidity/mortality were not noted. Conclusions: We conclude that secondary neutropenia is common after autologous stem cell transplant using the Plerixafor/GCSF combination for mobilization and is higher than reported in the literature (37% vs 10%). Patients who received this combination for mobilization should be followed up closely in the post-transplant period for secondary neutropenia. About half the patients who received the Benda-EAM conditioning regimen developed secondary neutropenia warranting its use with caution outside of a clinical trial.

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Immune Cell Profiling Reveals MAIT and Effector Memory CD4+ T Cell Recovery Link to Control of Cytomegalovirus Reactivation after Stem Cell Transplant

10.1101/2021.08.09.455593 ◽

2021 ◽

Author(s):

Lauren Stern ◽

Helen M McGuire ◽

Selmir Avdic ◽

Barbara Fazekas Fazekas de St Groth ◽

David Gottlieb ◽

...

Keyword(s):

Stem Cell ◽

Immune Reconstitution ◽

Immune Cell ◽

Haematopoietic Stem Cell ◽

Effector Memory ◽

Cell Transplant ◽

Post Transplant ◽

Low Level ◽

High Level ◽

Mait Cell

Human cytomegalovirus (HCMV) reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we used mass cytometry to comprehensively define global patterns of innate and adaptive immune cell reconstitution at key phases of HCMV reactivation (before detection, initial detection, peak and near resolution) in the first 100 days post-transplant. In addition to identifying patterns of immune reconstitution in those with or without HCMV reactivation, we found mucosal-associated invariant T (MAIT) cell levels at the initial detection of HCMV DNAemia distinguished patients who subsequently developed low-level versus high-level HCMV reactivation. In addition, early recovery of effector-memory CD4+ T cells distinguished low-level and high-level reactivation. Our data describe distinct immune signatures that emerged with HCMV reactivation post-HSCT, and highlight MAIT cell levels at the initial detection of reactivation as a potential prognostic marker to guide clinical decisions regarding pre-emptive therapy.

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