L.P. Koh

A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation

Summary:We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I–IV mucositis was decreased in the group that received amifostine (P=0.02). Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.

Successful treatment of primary granulocytic sarcoma by non-myeloablative stem cell transplant

Pre-leukemic granulocytic sarcoma (GS) may pose an initial diagnostic problem and its therapeutic approach has never been formally established. To our knowledge, non-myeloablative stem cell transplantation has been reported in cases of leukemic GS, but not in primary GS. We report a case of primary GS with extensive and aggressive presenting features and successfully treated with intensive chemotherapy followed by non-myeloablative allogeneic stem cell transplant. This resulted in complete remission with minimal complications. Our case demonstrates the potential of graft-vs.-tumour effect in the treatment of GS and suggests that non-myeloablative allogeneic stem cell transplant may be a feasible therapeutic approach for primary GS.

Severe conidiobolomycosis complicating induction chemotherapy in a patient with acute lymphoblastic leukaemia

The patient, a 20-year-old male, was a full-time soldier and actively involved in field training when diagnosed with acute lymphoblastic leukaemia. Induction chemotherapy, consisting of vincristine, cyclophosphamide, adriamycin and dexamethasone, was given together with itraconazole 200 mg q.i.d. as fungal prophylaxis. He became neutropenic 13 d after commencing chemotherapy and on d15, developed acute onset of right facial and cervical swelling associated with stridor, which required endoscopic-guided intubation to protect his airways. A contrast-enhanced computed tomography (top left) showed the presence of a large right paratonsillar abscess with inflammatory response extending to the right masseter and parotid spaces, resulting in airway obstruction. He subsequently developed a collapse of the entire left lung because of an obstructive plaque in the left main stem bronchus (top right). A bronchoscopic biopsy of the lesion was initially suggestive of aspergillus tracheobronchitis and empirical treatment with caspofungin was commenced, as the concomitant occurrence of acute renal failure and ischemic hepatitis precluded the use of amphotericin or voriconazole. The patient made a striking recovery and was extubated 4 d later with an associated recovery of neutrophils. However, the correct diagnosis was only established when the causative organism was identified as Conidiobolus coronatus. Microscopically (bottom), sporangiola producing secondary multiplicative spores were seen. Conidiobolus coronatus is a saprophyte in soil or organic debris in a tropical environment and typically causes localized nasal and soft tissue infections in animals and rarely in humans. There is still no consensus on the most appropriate anti-fungal treatment. The social background of a patient may play an important role in the pathogenesis of opportunistic infections in an immunocompromised host.

Imatinib mesylate (STI-571) given concurrently with nonmyeloablative stem cell transplantation did not compromise engraftment and resulted in cytogenetic remission in a patient with chronic myeloid leukemia in blast crisis

Summary:The main obstacles to successful hematopoietic stem cell transplantation for patients with chronic myeloid leukemia (CML) in blast crisis (BC) are increased post-transplant relapse and high treatment-related mortality. We report a patient with CML in BC who was treated initially with imatinib mesylate and was then concurrently treated with a nonmyeloablative stem cell transplant. Successful engraftment of donor cells followed by complete cytogenetic remission was achieved in the absence of severe therapy-related toxicities. This case demonstrates that imatinib mesylate given through nonmyeloablative transplant is a minimally toxic therapeutic approach, which does not compromise engraftment and may result in a favorable outcome in patients with CML in BC.

Stem cell transplantation programme at Singapore General Hospital

The adult transplant programme at Singapore General Hospital (SGH) was established in 1985 and more than 820 transplants have been performed to date. An average of about 60 adult transplants (autologous and allogeneic) are performed each year. Transplants offered at SGH run the range from autologous to mismatched cord and unrelated transplants. Special interests of the transplant programme include non-myeloablative transplants in aplastic anaemia, cell therapy protocols including cytokine-induced killer cells, patterns of GVHD, cord blood transplantation for autoimmune diseases and graft engineering. A cGMP (good manufacturing practice) cell therapy laboratory was recently established to facilitate bench-to-bedside translational cell therapy trials. A BMT consortium has been formed among the various paediatric and adult transplant centres for harmonization of protocols and research activities.

Long‐term renal outcome after allogeneic hemopoietic stem cell transplant: A comprehensive analysis of risk factors in an Asian patient population

Allogeneic hemopoietic stem cell transplantation (allo‐HSCT) poses a significant challenge to renal function due to multiple drug‐ and complication‐related renal toxicity. In this single‐center series of 216 adult Asian patients with a long and complete follow‐up, 41 developed chronic kidney disease (CKD) giving a cumulative incidence of 19.0% at 25 years (median follow‐up duration 7.84 years, range 2.0‐27.7 years), but only two of the 41 patients reached stage 4 CKD and another two required dialysis. In contrast, acute kidney injury occurred in most patients, where glomerular filtration rate (GFR) suffered a mean fall of 50 mL/min/1.73 m2 at 6 months post‐transplant compared with baseline. Suppression of renal function may last beyond 6 months but is potentially reversible, although not to baseline level in most patients. Analysis of a comprehensive range of 18 risk factors showed that older age, lower GFR at transplant, unrelated donor, diagnosis of AML, presence of diabetes mellitus at transplant, and duration of foscarnet use were significantly associated with CKD development, with the first three remaining as independent risks for CKD in multivariate analysis. Long‐term survival is not affected by renal function, being 78.6% as compared to 85.5% for patients with low vs normal GFR at 2 years, respectively.