Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs. controls (p=0.0004). After controlling for significant variables, proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs. matched controls (p<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.

Summary:Fanconi anemia (FA), a rare autosomal recessive disease, frequently evolves to bone marrow failure and acute myeloid leukemia, and BMT is the treatment of choice for patients with FA. However, their exquisite hypersensitivity to DNA cross-linking agents is associated with severe complications and several investigators have been looking for the ideal preparatory regimen. We have been involved in a program of progressively decreasing doses of cyclophosphamide (CY) as conditioning therapy, in an attempt to identify the lowest dose of CY capable of maintaining the graft with minimum complications. Here, we describe our experience of allogeneic BMT offered to 16 patients with FA and an HLA-compatible sibling donor, conditioned with 100 mg/kg of CY. The actuarial survival is 88% at approximately 37 months. Mucositis у grade II was the most common complication (94%), followed by bacteremias (38%). Veno-occlusive disease and hemorrhagic cystitis did not occur. Sustained engraftment was obtained in 94% of patients, and acute and chronic GVHD was diagnosed in 13% and 7%, respectively. The lowest dose of CY for transplant in FA patients is yet to be determined, but further reductions seem possible.

Summary Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen‐matched related donors. Methotrexate and cyclosporine were given for graft‐versus‐host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2–3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44–58) months and 16 (3–52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.

-We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (hsct). central nervous system (cNs) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and cNs infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. the most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.KEY WORDs: neurological complications, hematopoietic stem cell transplantation, stem-cell transplantation. Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH): estudo retrospectivo em um centro de TCTH no BrasilResumo -Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (tcth). As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia.PALAvRAs-chAvE: complicações neurológicas, transplante de células tronco hematopoiéticas, transplante de precursores hematopoiéticos.