Fred Rosner

Immune Deficiency Syndrome in Children

The present epidemic of acquired immune deficiency syndrome (AIDS) was originally described in homosexual men and subsequently in intravenous drug abusers, Haitians, and hemophiliacs. Profound defects in cell-mediated immunity (CMI) are associated with Kaposis sarcoma and a variety of serious opportunistic infections. Recently, we and others have encountered a group of children with an otherwise unexplained immune deficiency syndrome and infections of the type found in adults with AIDS. In this report, we describe eight children from the Newark, NJ, metropolitan area born into families with recognized risks for AIDS. These patients have had recurrent febrile illnesses, failure to thrive, hypergammaglobulinemia, and depressed CMI. Four of these children have died. Our experience suggests that children living in high-risk households are susceptible to AIDS and that sexual contact, drug abuse, or exposure to blood products is not necessary for disease transmission.

Hodgkin's disease and acute leukemia: Report of eight cases and review of the literature☆

Eight cases of Hodgkins disease and acute leukemia are reported. An additional 74 cases of acute myelocytic leukemia or one of its variants, 11 cases of acute lymphocytic leukemia, 12 cases of chronic myelocytic leukemia and 37 cases of chronic lymphocytic leukemia associated with Hodgkins disease are reviewed from the literature. In 3 of the 82 patients with acute myelocytic leukemia and Hodgkins disease, the two diseases occurred simultaneously. Of the remaining 79 patients, 76 had received radiation therapy for their Hodgkins disease and acute myelocytic leukemia had developed 1.2 to 19 years later (mean 6.5 years). Thirty-four of these patients also received antineoplastic chemotherapy. Only three patients with Hodgkins disease were treated with multiple chemotherapy alone; in these, Hodgkins disease developed 1.2, 1.5 and 3.2 years later. In 4 of 11 patients with acute lymphocytic leukemia and Hodgkins disease, the two disorders occurred simultaneously. The other seven patients were all treated with radiation for their Hodgkins disease, and acute lymphocytic leukemia developed 2 to 8 years later (mean 4.5 years). Three of the 7 patients also received alkylating agents. It is concluded that the development of acute leukemia, mostly acute myelocytic leukemia but also acute lymphocytic leukemia, during the course of Hodgkins disease, is most likely related to radiation therapy. There is as yet insufficient evidence to implicate intensive chemotherapy in the causation of acute leukemia since in only three patients with Hodgkins disease treated with chemotherapy alone has the development of acute leukemia been reported. It is possible, however, that chemotherapy potentiates the effect of radiotherapy. 2t is also possible that acute leukemia is part of the natural history of Hodgkins disease and is occurring with greater frequency because of improved survival in Hodgkins disease since the introduction of better radiotherapeutic and chemotherapeutic treatment regimens.

Multiple Myeloma Terminating in Acute Leukemia Report of 12 Cases and Review of the Literature

Abstract Twelve cases of multiple myeloma and acute leukemia are reported and an additional 46 cases from the literature are reviewed. In 11 instances, both diseases occurred simultaneously; in 1 case, the diagnosis of acute leukemia cannot be substantiated. In all the remaining 46 patients with multiple myeloma, acute myeloblastic or myelomonocytic leukemia, or a variant thereof, developed. There were no cases of lymphoblastlc leukemia. In 6 cases, no sex was indicated; in the remaining 40, 26 were men and 14 women. Nineteen patients received melphalan therapy only for 22 to 102 months, seemingly implicating this drug in the development of acute leukemia 36 to 147 months later. Twenty-five patients received melphalan as well as other cytotoxic and/or irradiation treatment. Three patients received no melphalan at all. Acute leukemia may be part of the natural history of multiple myeloma and may be seen with increasing frequency because of the longer survival of patients with multiple myeloma since the introduction of melphalan. Late death from acute leukemia after a definite remission, often lasting years, from multiple myeloma is thought to be preferable to early death without remission.

Babesiosis in splenectomized adults: Review of 22 reported cases

Since 1957, there have been 22 reported cases of human babesiosis in splenectomized persons, representing about one third of all clinical human babesiosis. Splenectomy had been performed one month to 36 years (mean 8.7 years, median 6.0 years) earlier for a variety of reasons. Four of the seven European cases were from Babesia divergens whereas 12 of the 15 United States cases were from B. microti. Most of the 22 patients had moderate to severe clinical disease including hemolytic anemia, yet all but six recovered. Three patients had transfusion-acquired babesiosis. Treatments employed included the use of chloroquine, quinine, pyrimethamine, pentamidine, clindamycin, dialysis, and exchange transfusion. Splenectomized and/or otherwise immunocompromised hosts should be advised to avoid visiting endemic areas for babesiosis such as Nantucket Island or Marthas Vineyard in Massachusetts and Shelter Island and other parts of Long Island, New York. Babesiosis must be considered as one of the not uncommon organisms responsible for the postsplenectomy sepsis syndrome and one for which there is no current prophylaxis.

Acute myeloid leukemia following treatment of hodgkin's disease. A review

Risk factors were analyzed and searched for possible predictive parameters for the development of acute myeloid leukemia in 216 reported patients previously treated for Hodgkins disease. The distribution of histologic subtypes and the stage at diagnosis were similar to that of all patients with Hodgkins disease. Seventy‐five percent of the 216 patients in whom acute myeloid leukemia developed had received both radiotherapy and chemotherapy, 15% chemotherapy only, and 10% radiotherapy only. Of those receiving radiotherapy, 66% were given multiple courses or total nodal irradiation. Of the patients receiving chemotherapy, 77% had received more than eight months of single or combination drug therapy; only 4% had not been exposed to alkylating agents. When acute leukemia developed, 68% of the patients showed no clinical or pathologic evidence of residual Hodgkins disease. A period of pancytopenia preceded the onset of overt leukemia in at least one‐third of the patients. Complete or partial remission of the acute leukemia was achieved in 25% of the patients treated with antileukemic chemotherapy. On the basis of these findings, it is deemed advisable to reexamine the intensity of treatment presently being administered to achieve cure of Hodgkins disease. Unnecessary or unproved programs of combined radiation therapy and chemotherapy should be avoided. An optimal balance between the risks and benefits of treatment needs to be applied.

Acute leukemia as a delayed consequence of cancer chemotherapy

Acute myelocytic leukemia occurring many years after intensive radiotherapy and/or chemotherapy has been reported in 82 patients with Hodgkins disease, 58 patients with multiple myeloma, and 40 patients with chronic lymphocytic leukemia. The precise incidence of this occurrence is uncertain, since the total number of patients at risk is unknown. Most patients with Hodgkins disease had received intensive radiation therapy. Many also received chemotherapy. One‐third of the patients with myeloma were treated only with melphalan. Acute leukemia may occur as part of the natural history of Hodgkins disease and multiple myeloma; it has been seen with increasing frequency in recent years due to improved survival secondary to better treatment. It is also possible that radiotherapy and/or chemotherapy may be causally related to the development of acute leukemia.

Hemophilia in the Talmud and Rabbinic Writings

Abstract A familial bleeding disorder, probably hemophilia, is described in the Talmud. The decree of Rabbi Judah that the sibling of two brothers who died of bleeding after circumcision may not be...

Non‐Hodgkin's lymphoma and acute myeloblastic leukemia. A report of 12 cases and review of the literature

Twelve cases of non‐Hodgkins lymphoma and acute myeloblastic leukemia or one of its variants are reported. An additional 33 cases from the literature are reviewed. The mean interval between the diagnosis of lymphoma and acute leukemia is 5.2 years. In 5 patients the two diseases occurred simultaneously or within 6 months of each other. All but 10 of the 45 patients received radiation therapy for their lymphoma. Nine patients had either total nodal or total body irradiation or both. Eight patients received chemotherapy alone. No patient was untreated. Survival after the diagnosis of acute leukemia ranged from 3 days to 14 months, with a median of 3 months. Four patients achieved complete hematological remission following antileukemic therapy. Acute leukemia is estimated to occur in patients with non‐Hodgkins lymphoma in New York State with a 37‐fold increased frequency over the expected number. Although acute leukemia may occur in a higher than expected frequency in patients with non‐Hodgkins lymphoma because of an increased risk of a second neoplasm in patients with a primary tumor, it seems more likely that the acute leukemia may be related to the radiotherapy and/or chemotherapy administered to treat the lymphoma. Late death from leukemia after chemotherapeutic or radiotherapeutic remission of advanced non‐Hodgkins lymphoma is preferable to morbidity and/or early death from untreated or inadequately treated lymphoma.

Second neoplasms in acute lymphoblastic leukemia

The authors reviewed 61 reported cases of second neoplasms in acute lymphoblastic leukemia (ALL), including 17 patients with ALL followed by another type of acute leukemia, 12 patients with ALL followed by chronic myelocytic leukemia, 19 patients with ALL followed by lymphoma, and 13 patients with ALL followed by other solid tumors. From a review of the literature, it is believed that there is no firm evidence yet that patients with ALL, intensively treated with chemotherapy and/or radiotherapy, are at increased risk of developing therapy‐related second neoplasms. Because the number of cases reported is small, there is even insufficient data to firmly suggest that acute myeloblastic leukemia, following intensive therapy for ALL, occurs in a higher‐than‐expected frequency.

The ethics of randomized clinical trials

Randomized clinical trials pose a number of fundamental ethical problems to which morally sensitive investigators must give careful consideration. The randomized double-blind clinical trial is ethically justified and the preferred method of demonstrating therapeutic effectiveness and safety. Alternate methods such as crossover and self-controlled designs, the use of historical controls, observational methods, and practitioners clinical trials also exist and have their place in certain circumstances. The use of randomized double-blind clinical trials must assure adequate explanation of the research plan to the patient, the documentation of informed consent, adequate consideration of safety, and an acceptably low risk/benefit ratio.