Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in -vitro sensitivity data and clinical response to empirical antibiotic therapy.

OBJECTIVE: To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Paediatric bone marrow transplant unit at Bismillah Taqee Institute of Health Sciences and Blood Disease Center from September 1999 to May 2004. PATIENTS AND METHODS: All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. RESULTS: Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. CONCLUSION: Gram-negative infections predominated, Imipenem/ Amikacin found to be most effective therapy while a low mortality rate is recorded in our setting suggesting good infection control.

In-vivo purging with the anti-CD20 antibody rituximab along with standard allogeneic peripheral blood stem cell transplantation (PBSCT) for relapsed childhood pre-B acute lymphoblastic leukaemia (ALL).

This case report describes the use of Rituximab for in vivo purging (by intravenous infusion) in a 12 years old boy with second remission of pre-B ALL. It was followed by conditioning therapy consisted of Busulphan and Cyclophosphamide. rh-G-CSF primed stem cells from an HLA identical sibling donor were infused. Standard graft versus host disease prophylaxis was given. He engrafted within two weeks. He did not develop acute graft versus host disease (aGvHD) but localized chronic GvHD developed. He had been on regular follow-up at CMH, Rawalpindi and is in complete remission 13 months post-PBSCT with no evidence of chronic GvHD at present.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

OBJECTIVE: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. DESIGN: A single centre descriptive study. PLACE AND DURATION OF STUDY: Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. PATIENTS AND METHODS: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. RESULTS: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. CONCLUSION: Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.