Thrombotic microangiopathic nephropathy, pulmonary hypertension and nephromegaly: case report of a patient treated with endothelin receptor antagonist

The coexistence of thrombotic microangiopathic nephropathy and pulmonary hypertension has only been described in association with malignancy and its treatment. Here we describe a 14-year-old boy with no prior medical history who presented with hypertension, proteinuria and nephromegaly, and then developed progressive pulmonary hypertension. Renal histology showed lesions consistent with glomerulopathy due to thrombotic microangiopathy (TMA). Pulmonary hypertension was controlled by the use of an oral endothelin receptor antagonist (bosentan). Although renal function deteriorated at the onset of pulmonary hypertension, an improvement was observed after the bosentan treatment. Nephromegaly persisted, but current creatinine clearance values are within the normal range. While this case exemplifies how thrombotic microangiopathic nephropathy may be associated with pulmonary hypertension, a therapeutic role of endothelin antagonists is suggested, not only for pulmonary hypertension but also for microangiopathic nephropathy.     

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia during first complete remission

Patients with acute lymphoblastic leukemia who have poor prognostic features at diagnosis usually have a short disease-free survival in spite of successful remission induction. Those poor risk features are: age over 30 years, a white blood cell count over 25,000/microliter, certain translocations of chromosomes, and requirement for more than six weeks of induction chemotherapy to attain a complete remission. We have used high-dose radiochemotherapy to prepare 39 patients with acute lymphoblastic leukemia in first complete remission (1 infant and 38 adults; median age 23 years) for bone marrow transplantation from histocompatible sibling donors. Thirty-one of the 39 patients in this study had one (n = 23) or more (n = 8) poor risk features: age (n = 7); high white blood cell count (n = 19); translocations (n = 4), or resistance to initial induction therapy (n = 11). Currently, 26 patients are surviving for 4-72 months (median 18 months) following marrow grafting and are in complete remission. One of the surviving patients had two marrow transplant procedures because of recurrent leukemia. Actuarial survival in complete remission is 63% for the entire group of 39 patients and is 60% if the eight patients who had no poor risk features are excluded from analysis. The following causes for failure were observed: leukemic relapse was encountered in four patients between 3 and 17 months after BMT for an actuarial relapse rate of 16%; bacterial sepsis was the cause of death in two patients; graft-versus-host disease and/or interstitial pneumonia led to the demise of seven patients, and one patient died with leukoencephalopathy. It appears that high-dose radiochemotherapy followed by bone marrow transplantation from a histocompatible sibling donor during first complete remission can result in a high disease-free survival rate for younger adults with poor-risk acute lymphoblastic leukemia. This concept needs to be tested in prospective trials comparing bone marrow transplantation with chemotherapy.     

Immunotoxins for ex vivo marrow purging in autologous bone marrow transplantation for acute nonlymphocytic leukemia

Two potent antimyeloid immunotoxins (IT) were generated by conjugating AML-2-23 (anti-CD14) and MCS-2 (anti-CD13) monoclonal antibodies (mAb) to the ribosome-inactivating phytotoxin, ricin. Both IT selectively bound to target cells, inhibited protein synthesis, and prevented the clonogenic growth of fresh marrow blasts from acute nonlymphocytic leukemia patients as well as KG-1 (ANLL) cells. Cryopreservation did not inhibit IT activity. We conclude that AML-2-23-ricin and MCS-2-ricin show potential for effective ex vivo marrow purging in autologous bone marrow transplantation (ABMT) for ANLL. To our knowledge, this study represents the first evidence of the clinical potential of IT in high-risk ANLL.     

Hemolytic uremic syndrome following bone marrow transplantation: a case report and review of the literature

Unlike primary idiopathic childhood hemolytic uremic syndrome (HUS), certain cases of HUS are clearly secondary. This article describes a child who represents the 11th reported case of secondary HUS following bone marrow transplantation, and notably, the fourth such case without exposure to cyclosporine A. The renal biopsy was diagnostic in this case. Therefore, the pathognomonic features of the biopsy, as well as its prognostic implications are described and clarified. This patient was treated with plasma exchange, and is the second reported surviving case of secondary HUS following bone marrow transplantation.     

Osteonecrosis of the talus of a child with acute lymphoblastic leukemia: A case report

Osteonecrosis (ON) is a disabling complication of acute lymphoblastic leukemia (ALL) treatment in children and young adults. Isolated talus involvement is thought to be uncommon. A unique case of a 11-year-old female patient with ON in her left talus which developed six months after the completion of chemotherapy that she received for ALL is reported. A conservative treatment protocol was followed including activity modification, analgesia and prevention of weight-bearing. However, the disease significantly progressed during follow-up period. The present study makes an important contribution to the literature with unusual involvement pattern and location of ON after ALL treatment and with a long follow-up duration.Level of evidenceIV.     

Pulmonary hypertension associated with pulmonary occlusive vasculopathy after allogeneic bone marrow transplantation

BACKGROUND: Pulmonary vasculature abnormalities, including pulmonary veno-occlusive disease, have been demonstrated in marrow allograft recipients. However, it is often difficult to make a correct diagnosis of pulmonary lesions. METHODS: An open lung biopsy was performed on a patient who developed severe pulmonary hypertension after bone marrow transplantation for T-cell lymphoma. RESULTS: An open lung biopsy specimen demonstrated pulmonary arterial occlusion due to intimal fibrosis and veno-occlusion. The most striking alteration was partial to complete occlusion of the small arteries by fibrous proliferation of the intima. CONCLUSION: High-dose preparative chemotherapy and radiation before transplantation are thought to have contributed to the development of vasculopathy in this patient, because arterial occlusion by intimal fibrosis and atypical veno-occlusion are often associated with lung injury due to chemoradiation. An open lung biopsy is essential for diagnosing pulmonary vascular disease presenting signs compatible with posttransplantation pulmonary hypertension.     

Autologous bone marrow transplantation in patients with adult acute leukemia in relapse.

Nine patients with adult acute leukemia were treated in relapse with piperazinedione plus supralethal total body irradiation in conjunction with autologous marrow infusion. Bone marrow cells were collected and stored in first remission. Storage time varied from 3 to 23 months. Before storage, marrow cells were separated using density albumin gradients in order to reduce the number of leukemic cells in the graft. Three patients died before day 14 after transplantation because of complications already present at the time of transplantation. In six patients, hemopoietic recovery started to occur within 14 days after transplantation. In four patients leukemia-free periods were obtained, lasting 60+ days. The three patients with the longest leukemia-free period after transplantation (range 75 to 220+ days) are reported in more detail. One patient is still alive without evidence of leukemia, with full hematological recovery 220+ days after transplantation.     

On a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia

The Authors describe the case of a 14-year-old girl who developed a multifocal osteonecrosis (ON), after treatment with chemotherapy and corticosteroids for acute lymphoblastic leukemia (ALL). She came to our attention about 6 months after the beginning of treatment complaining of pain in her left knee and later in both hips and shoulders. Radiography and MRI confirmed the presence of avascular ON at all these sites. The patient underwent bilateral total hip arthroplasty, which was still functioning well at the last follow-up visits at 5 years, and at 5 years and 4 months. ON is increasingly recognized as a complication of the treatment of cancer in children and adolescents, and as patients now frequently survive ALL into adulthood, orthopedists will be increasingly called on to manage this complication affecting multiple joints in children and young adults.