Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease.

The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.

Unrelated cord blood transplantation vs matched unrelated donor bone marrow transplantation: the risks and benefits of each choice.

Matched sibling BMT is the treatment of choice for many malignant and non-malignant diseases. Unfortunately, donor availability limits its applicability with only approximately one-third of patients having HLA-matched family members. For the remaining two-thirds of patients who need an allogeneic procedure, an alternative donor is required. Matched unrelated donor (MUD) bone marrow transplants have proven useful for many of these patients, however, matched donors may be unavailable or too time-consuming to find. In addition, MUD transplants are associated with high morbidity and mortality secondary to severe graft-versus-host disease (GVHD), organ toxicity, and infections. For those patients without a matched related or unrelated volunteer donor, unrelated umbilical cord blood transplantation (UCBT) is a feasible alternative. UCBT has been associated with a lower incidence and severity of GVHD than MUD BMT, allowing successful transplantation in the HLA-mismatched setting, thus increasing the donor pool. This manuscript reviews the available literature regarding these two procedures, assesses their risk/benefit ratio, and arrives at several conclusions regarding their relative indications.

Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma.

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+) cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.

Myelodysplastic syndrome presenting with clonal rearrangement isolated to chromosomal region 1q.

Myelodysplastic syndrome (MDS) is a malignant hematologic disorder that may present with clinical features consistent with the diagnosis of severe aplastic anemia (SAA). Distinguishing the two disorders may depend on the presence of a clonal chromosomal abnormality. In the following, we report a case of MDS associated with what we believe to be a previously unreported clonal abnormality of chromosome 1q, a finding that enabled us to distinguish between MDS and SAA.

Steroid-refractory cutaneous graft-versus-host disease after transplantation of haploidentical parental CD34+ cells in children with Down's syndrome and recurrent acute leukemia.

PURPOSE: This study evaluated the feasibility of performing haploidentical CD34+ selected transplants for children with Down's syndrome (DS) and recurrent leukemia. PATIENTS AND METHODS: Within a cohort of 15 children, two patients had DS. Transplantation of CD34+ cells from haploidentical parents was performed after the children were conditioned with fractionated total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate. RESULTS: The preparative regimen was well tolerated, and engraftment of polymorphonuclear cells and platelets took place promptly (by day 20) in both patients with DS. However, both patients with DS experienced severe grade IV GVHD that was limited to the skin and was refractory to salvage with high-dose methylprednisolone therapy. In one patient, GVHD responded to second-line salvage therapy with ATG, but the patient died on day 234 from leukemic relapse. The second patient had GVHD that did not respond to ATG and died of multisystem organ failure and refractory GVHD on day 44. Two of two DS patients had steroid refractory severe acute GVHD of the skin, while only one of 11 evaluated and identically treated non-DS patients had severe GVHD (p < 0.05). CONCLUSION: These observations in patients who underwent mismatched bone marrow transplantation suggests that patients with DS have an increased risk of severe acute GVHD of the skin in this context.

Langerhans' cell histiocytosis presenting with the superior vena cava syndrome: a case report.

A case of Langerhans' cell histiocytosis confined to the mediastinum and presenting with de novo superior cava syndrome is reported. The causes of superior vena cava syndrome in childhood are discussed as is the importance of obtaining pathologic diagnosis prior to initiating therapy.